1932

Abstract

Controlled assembly and disassembly of multi-protein complexes is central to cellular signaling. Proteins of the widespread and functionally diverse HORMA family nucleate assembly of signaling complexes by binding short peptide motifs through a distinctive safety-belt mechanism. HORMA proteins are now understood as key signaling proteins across kingdoms, serving as infection sensors in a bacterial immune system and playing central roles in eukaryotic cell cycle, genome stability, sexual reproduction, and cellular homeostasis pathways. Here, we describe how HORMA proteins’ unique ability to adopt multiple conformational states underlies their functions in these diverse contexts. We also outline how a dedicated AAA+ ATPase regulator, Pch2/TRIP13, manipulates HORMA proteins’ conformational states to activate or inactivate signaling in different cellular contexts. The emergence of Pch2/TRIP13 as a lynchpin for HORMA protein action in multiple genome-maintenance pathways accounts for its frequent misregulation in human cancers and highlights TRIP13 as a novel therapeutic target.

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2022-06-21
2024-12-10
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Literature Cited

  1. 1.
    Aravind L, Koonin EV. 1998. The HORMA domain: a common structural denominator in mitotic checkpoints, chromosome synapsis and DNA repair. Trends Biochem. Sci. 23:284–86
    [Google Scholar]
  2. 2.
    Mapelli M, Musacchio A. 2007. MAD contortions: Conformational dimerization boosts spindle checkpoint signaling. Curr. Opin. Struct. Biol. 17:716–25
    [Google Scholar]
  3. 3.
    Skinner JJ, Wood S, Shorter J, Englander SW, Black BE. 2008. The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching. J. Cell Biol. 183:761–68
    [Google Scholar]
  4. 4.
    Luo X, Yu H. 2008. Protein metamorphosis: the two-state behavior of Mad2. Structure 16:1616–25
    [Google Scholar]
  5. 5.
    Yang M, Li B, Tomchick DR, Machius M, Rizo J et al. 2007. p31comet blocks Mad2 activation through structural mimicry. Cell 131:744–55
    [Google Scholar]
  6. 6.
    Jao CC, Ragusa MJ, Stanley RE, Hurley JH 2013. A HORMA domain in Atg13 mediates PI 3-kinase recruitment in autophagy. PNAS 110:5486–91
    [Google Scholar]
  7. 7.
    Suzuki H, Kaizuka T, Mizushima N, Noda NN 2015. Structure of the Atg101–Atg13 complex reveals essential roles of Atg101 in autophagy initiation. Nat. Struct. Mol. Biol. 22:572–80
    [Google Scholar]
  8. 8.
    Hegedus K, Nagy P, Gaspari Z, Juhasz G. 2014. The putative HORMA domain protein Atg101 dimerizes and is required for starvation-induced and selective autophagy in Drosophila. Biomed. Res. Int. 2014.470482
    [Google Scholar]
  9. 9.
    Qi S, Kim DJ, Stjepanovic G, Hurley JH. 2015. Structure of the human Atg13–Atg101 HORMA heterodimer: an interaction hub within the ULK1 complex. Structure 23:1848–57
    [Google Scholar]
  10. 10.
    Burroughs AM, Zhang D, Schaffer DE, Iyer LM, Aravind L. 2015. Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling. Nucleic Acids Res 43:10633–54
    [Google Scholar]
  11. 11.
    Ye Q, Lau RK, Mathews IT, Birkholz EA, Watrous JD et al. 2020. HORMA Domain proteins and a Trip13-like ATPase regulate bacterial cGAS-like enzymes to mediate bacteriophage immunity. Mol. Cell 77:709–22.e7
    [Google Scholar]
  12. 12.
    Clairmont CS, Sarangi P, Ponnienselvan K, Galli LD, Csete I et al. 2020. TRIP13 regulates DNA repair pathway choice through REV7 conformational change. Nat. Cell. Biol. 22:87–96
    [Google Scholar]
  13. 13.
    San-Segundo PA, Roeder GS. 1999. Pch2 links chromatin silencing to meiotic checkpoint control. Cell 97:313–24
    [Google Scholar]
  14. 14.
    Borner GV, Barot A, Kleckner N. 2008. Yeast Pch2 promotes domainal axis organization, timely recombination progression, and arrest of defective recombinosomes during meiosis. PNAS 105:3327–32
    [Google Scholar]
  15. 15.
    Joshi N, Barot A, Jamison C, Borner GV 2009. Pch2 links chromosome axis remodeling at future crossover sites and crossover distribution during yeast meiosis. PLOS Genet 5:e1000557
    [Google Scholar]
  16. 16.
    Wojtasz L, Daniel K, Roig I, Bolcun-Filas E, Xu H et al. 2009. Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLOS Genet 5:e1000702
    [Google Scholar]
  17. 17.
    Tipton AR, Wang K, Oladimeji P, Sufi S, Gu Z, Liu ST. 2012. Identification of novel mitosis regulators through data mining with human centromere/kinetochore proteins as group queries. BMC Cell Biol 13:15
    [Google Scholar]
  18. 18.
    Wang K, Sturt-Gillespie B, Hittle JC, Macdonald D, Chan GK et al. 2014. Thyroid hormone receptor interacting protein 13 (TRIP13) AAA-ATPase is a novel mitotic checkpoint-silencing protein. J. Biol. Chem. 289:23928–37
    [Google Scholar]
  19. 19.
    Ye Q, Rosenberg SC, Moeller A, Speir JA, Su TY, Corbett KD 2015. TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching. eLife 4:e07367
    [Google Scholar]
  20. 20.
    Eytan E, Wang K, Miniowitz-Shemtov S, Sitry-Shevah D, Kaisari S et al. 2014. Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31comet. PNAS 111:12019–24
    [Google Scholar]
  21. 21.
    Miniowitz-Shemtov S, Eytan E, Kaisari S, Sitry-Shevah D, Hershko A. 2015. Mode of interaction of TRIP13 AAA-ATPase with the Mad2-binding protein p31comet and with mitotic checkpoint complexes. PNAS 112:11536–40
    [Google Scholar]
  22. 22.
    Ma HT, Poon RYC. 2016. TRIP13 regulates both the activation and inactivation of the spindle-assembly checkpoint. Cell Rep 14:1086–99
    [Google Scholar]
  23. 23.
    Ye Q, Kim DH, Dereli I, Rosenberg SC, Hagemann G et al. 2017. The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding. EMBO J 36:2419–34
    [Google Scholar]
  24. 24.
    Ma HT, Poon RYC. 2018. TRIP13 functions in the establishment of the spindle assembly checkpoint by replenishing O-MAD2. Cell Rep 22:1439–50
    [Google Scholar]
  25. 25.
    Kim DH, Han JS, Ly P, Ye Q, McMahon MA et al. 2018. TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC. Nat. Commun. 9:4354
    [Google Scholar]
  26. 26.
    Tromer EC, van Hooff JJE, Kops G, Snel B 2019. Mosaic origin of the eukaryotic kinetochore. PNAS 116:12873–82
    [Google Scholar]
  27. 27.
    Mapelli M, Massimiliano L, Santaguida S, Musacchio A 2007. The Mad2 conformational dimer: structure and implications for the spindle assembly checkpoint. Cell 131:730–43
    [Google Scholar]
  28. 28.
    Kim BW, Jin Y, Kim J, Kim JH, Jung J et al. 2018. The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation. Autophagy 14:2104–16
    [Google Scholar]
  29. 29.
    Liang L, Feng J, Zuo P, Yang J, Lu Y, Yin Y 2020. Molecular basis for assembly of the shieldin complex and its implications for NHEJ. Nat. Commun. 11:1972
    [Google Scholar]
  30. 30.
    Hara M, Ozkan E, Sun H, Yu H, Luo X 2015. Structure of an intermediate conformer of the spindle checkpoint protein Mad2. PNAS 112:11252–57
    [Google Scholar]
  31. 31.
    Puchades C, Sandate CR, Lander GC. 2020. The molecular principles governing the activity and functional diversity of AAA+ proteins. Nat. Rev. Mol. Cell Biol. 21:43–58
    [Google Scholar]
  32. 32.
    Sauer RT, Baker TA. 2011. AAA+ proteases: ATP-fueled machines of protein destruction. Annu. Rev. Biochem. 80:587–612
    [Google Scholar]
  33. 33.
    Alfieri C, Chang L, Barford D 2018. Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. Nature 559:274–78
    [Google Scholar]
  34. 34.
    Brulotte ML, Jeong BC, Li F, Li B, Yu EB et al. 2017. Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing. Nat. Commun. 8:1956
    [Google Scholar]
  35. 35.
    Xie W, Wang S, Wang J, de la Cruz MJ, Xu G et al. 2021. Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex. PNAS 118:e2024512118
    [Google Scholar]
  36. 36.
    Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A et al. 2018. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 359:eaar4120
    [Google Scholar]
  37. 37.
    Gao L, Altae-Tran H, Bohning F, Makarova KS, Segel M et al. 2020. Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Science 369:1077–84
    [Google Scholar]
  38. 38.
    Wu J, Chen ZJ. 2014. Innate immune sensing and signaling of cytosolic nucleic acids. Annu. Rev. Immunol. 32:461–88
    [Google Scholar]
  39. 39.
    Davies BW, Bogard RW, Young TS, Mekalanos JJ 2012. Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence. Cell 149:358–70
    [Google Scholar]
  40. 40.
    Cohen D, Melamed S, Millman A, Shulman G, Oppenheimer-Shaanan Y et al. 2019. Cyclic GMP-AMP signalling protects bacteria against viral infection. Nature 574:691–95
    [Google Scholar]
  41. 41.
    Whiteley AT, Eaglesham JB, de Oliveira Mann CC, Morehouse BR, Lowey B et al. 2019. Bacterial cGAS-like enzymes synthesize diverse nucleotide signals. Nature 567:194–99
    [Google Scholar]
  42. 42.
    Millman A, Melamed S, Amitai G, Sorek R 2020. Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems. Nat. Microbiol. 5:1608–15
    [Google Scholar]
  43. 43.
    Lau RK, Ye Q, Birkholz EA, Berg KR, Patel L et al. 2020. Structure and mechanism of a cyclic trinucleotide-activated bacterial endonuclease mediating bacteriophage immunity. Mol. Cell 77:723–33.e6
    [Google Scholar]
  44. 44.
    Primorac I, Musacchio A. 2013. Panta rhei: the APC/C at steady state. J. Cell Biol. 201:177–89
    [Google Scholar]
  45. 45.
    King RW, Peters JM, Tugendreich S, Rolfe M, Hieter P, Kirschner MW 1995. A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81:279–88
    [Google Scholar]
  46. 46.
    Sudakin V, Ganoth D, Dahan A, Heller H, Hershko J et al. 1995. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol. Biol. Cell 6:185–97
    [Google Scholar]
  47. 47.
    Musacchio A. 2015. The molecular biology of spindle assembly checkpoint signaling dynamics. Curr. Biol. 25:R1002–18
    [Google Scholar]
  48. 48.
    Sudakin V, Chan GK, Yen TJ 2001. Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J. Cell Biol. 154:925–36
    [Google Scholar]
  49. 49.
    Kulukian A, Han JS, Cleveland DW. 2009. Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding. Dev. Cell 16:105–17
    [Google Scholar]
  50. 50.
    Corbett KD. 2017. Molecular mechanisms of spindle assembly checkpoint activation and silencing. Prog. Mol. Subcell. Biol. 56:429–55
    [Google Scholar]
  51. 51.
    Faesen AC, Thanasoula M, Maffini S, Breit C, Muller F et al. 2017. Basis of catalytic assembly of the mitotic checkpoint complex. Nature 542:498–502
    [Google Scholar]
  52. 52.
    Chen RH, Shevchenko A, Mann M, Murray AW. 1998. Spindle checkpoint protein Xmad1 recruits Xmad2 to unattached kinetochores. J. Cell Biol. 143:283–95
    [Google Scholar]
  53. 53.
    Moyle MW, Kim T, Hattersley N, Espeut J, Cheerambathur DK et al. 2014. A Bub1–Mad1 interaction targets the Mad1–Mad2 complex to unattached kinetochores to initiate the spindle checkpoint. J. Cell Biol. 204:647–57
    [Google Scholar]
  54. 54.
    London N, Biggins S. 2014. Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint. Genes Dev 28:140–52
    [Google Scholar]
  55. 55.
    Sironi L, Mapelli M, Knapp S, De Antoni A, Jeang KT, Musacchio A. 2002. Crystal structure of the tetrameric Mad1–Mad2 core complex: implications of a ‘safety belt’ binding mechanism for the spindle checkpoint. EMBO J 21:2496–506
    [Google Scholar]
  56. 56.
    De Antoni A, Pearson CG, Cimini D, Canman JC, Sala V et al. 2005. The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint. Curr. Biol. 15:214–25
    [Google Scholar]
  57. 57.
    Shah JV, Botvinick E, Bonday Z, Furnari F, Berns M, Cleveland DW. 2004. Dynamics of centromere and kinetochore proteins; implications for checkpoint signaling and silencing. Curr. Biol. 14:942–52
    [Google Scholar]
  58. 58.
    Yang M, Li B, Liu CJ, Tomchick DR, Machius M et al. 2008. Insights into Mad2 regulation in the spindle checkpoint revealed by the crystal structure of the symmetric Mad2 dimer. PLOS Biol 6:e50
    [Google Scholar]
  59. 59.
    Lara-Gonzalez P, Kim T, Oegema K, Corbett K, Desai A. 2021. A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores. Science 371:64–67
    [Google Scholar]
  60. 60.
    Piano V, Alex A, Stege P, Maffini S, Stoppiello GA et al. 2021. CDC20 assists its catalytic incorporation in the mitotic checkpoint complex. Science 371:67–71
    [Google Scholar]
  61. 61.
    Kamenz J, Hauf S. 2017. Time to split up: dynamics of chromosome separation. Trends Cell Biol 27:42–54
    [Google Scholar]
  62. 62.
    Ciosk R, Zachariae W, Michaelis C, Shevchenko A, Mann M, Nasmyth K. 1998. An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell 93:1067–76
    [Google Scholar]
  63. 63.
    Orth M, Mayer B, Rehm K, Rothweiler U, Heidmann D et al. 2011. Shugoshin is a Mad1/Cdc20-like interactor of Mad2. EMBO J 30:2868–80
    [Google Scholar]
  64. 64.
    Hellmuth S, Gomez HL, Pendas AM, Stemmann O. 2020. Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2. Nature 580:536–41
    [Google Scholar]
  65. 65.
    Luo X, Tang Z, Xia G, Wassmann K, Matsumoto T et al. 2004. The Mad2 spindle checkpoint protein has two distinct natively folded states. Nat. Struct. Mol. Biol. 11:338–45
    [Google Scholar]
  66. 66.
    Xia G, Luo X, Habu T, Rizo J, Matsumoto T, Yu H 2004. Conformation-specific binding of p31comet antagonizes the function of Mad2 in the spindle checkpoint. EMBO J 23:3133–43
    [Google Scholar]
  67. 67.
    Défachelles L, Russo AE, Nelson CR, Bhalla N. 2020. The conserved AAA-ATPase PCH-2TRIP13 regulates spindle checkpoint strength. Mol. Biol. Cell 31:2219–33
    [Google Scholar]
  68. 68.
    Nelson CR, Hwang T, Chen PH, Bhalla N 2015. TRIP13PCH-2 promotes Mad2 localization to unattached kinetochores in the spindle checkpoint response. J. Cell Biol. 211:503–16
    [Google Scholar]
  69. 69.
    Westhorpe FG, Tighe A, Lara-Gonzalez P, Taylor SS. 2011. p31comet-mediated extraction of Mad2 from the MCC promotes efficient mitotic exit. J. Cell Sci. 124:3905–16
    [Google Scholar]
  70. 70.
    Teichner A, Eytan E, Sitry-Shevah D, Miniowitz-Shemtov S, Dumin E et al. 2011. p31comet promotes disassembly of the mitotic checkpoint complex in an ATP-dependent process. PNAS 108:3187–92
    [Google Scholar]
  71. 71.
    Jia L, Li B, Warrington RT, Hao X, Wang S, Yu H 2011. Defining pathways of spindle checkpoint silencing: functional redundancy between Cdc20 ubiquitination and p31comet. Mol. Biol. Cell 22:4227–35
    [Google Scholar]
  72. 72.
    Hagan RS, Manak MS, Buch HK, Meier MG, Meraldi P et al. 2011. p31comet acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment. Mol. Biol. Cell 22:4236–46
    [Google Scholar]
  73. 73.
    Mo M, Arnaoutov A, Dasso M 2015. Phosphorylation of Xenopus p31comet potentiates mitotic checkpoint exit. Cell Cycle 14:3978–85
    [Google Scholar]
  74. 74.
    Hegemann B, Hutchins JR, Hudecz O, Novatchkova M, Rameseder J et al. 2011. Systematic phosphorylation analysis of human mitotic protein complexes. Sci. Signal. 4:rs12
    [Google Scholar]
  75. 75.
    Date DA, Burrows AC, Summers MK. 2014. Phosphorylation regulates the p31Comet-mitotic arrest-deficient 2 (Mad2) interaction to promote spindle assembly checkpoint (SAC) activity. J. Biol. Chem. 289:11367–73
    [Google Scholar]
  76. 76.
    Kaisari S, Shomer P, Ziv T, Sitry-Shevah D, Miniowitz-Shemtov S et al. 2019. Role of Polo-like kinase 1 in the regulation of the action of p31comet in the disassembly of mitotic checkpoint complexes. PNAS 116:11725–30
    [Google Scholar]
  77. 77.
    Lara-Gonzalez P, Moyle MW, Budrewicz J, Mendoza-Lopez J, Oegema K, Desai A 2019. The G2-to-M transition is ensured by a dual mechanism that protects cyclin B from degradation by Cdc20-activated APC/C. Dev. Cell 51:313–25.e10
    [Google Scholar]
  78. 78.
    Lee SH, McCormick F, Saya H. 2010. Mad2 inhibits the mitotic kinesin MKlp2. J. Cell Biol. 191:1069–77
    [Google Scholar]
  79. 79.
    O'Neill TJ, Zhu Y, Gustafson TA 1997. Interaction of MAD2 with the carboxyl terminus of the insulin receptor but not with the IGFIR. Evidence for release from the insulin receptor after activation. J. Biol. Chem. 272:10035–40
    [Google Scholar]
  80. 80.
    Choi E, Zhang X, Xing C, Yu H. 2016. Mitotic checkpoint regulators control insulin signaling and metabolic homeostasis. Cell 166:567–81
    [Google Scholar]
  81. 81.
    Marston AL, Amon A. 2004. Meiosis: cell-cycle controls shuffle and deal. Nat. Rev. Mol. Cell Biol. 5:983–97
    [Google Scholar]
  82. 82.
    Zickler D, Kleckner N. 1999. Meiotic chromosomes: integrating structure and function. Annu. Rev. Genet. 33:603–754
    [Google Scholar]
  83. 83.
    Hunter N. 2015. Meiotic recombination: the essence of heredity. Cold Spring Harb. Perspect. Biol. 7:a016618
    [Google Scholar]
  84. 84.
    Bhalla N, Dernburg AF. 2008. Prelude to a division. Annu. Rev. Cell Dev. Biol. 24:397–424
    [Google Scholar]
  85. 85.
    Keeney S, Lange J, Mohibullah N. 2014. Self-organization of meiotic recombination initiation: general principles and molecular pathways. Annu. Rev. Genet. 48:187–214
    [Google Scholar]
  86. 86.
    West AMV, Komives EA, Corbett KD. 2018. Conformational dynamics of the Hop1 HORMA domain reveal a common mechanism with the spindle checkpoint protein Mad2. Nucleic Acids Res 46:279–92
    [Google Scholar]
  87. 87.
    West AM, Rosenberg SC, Ur SN, Lehmer MK, Ye Q et al. 2019. A conserved filamentous assembly underlies the structure of the meiotic chromosome axis. eLife 8:e40372
    [Google Scholar]
  88. 88.
    Ferdous M, Higgins JD, Osman K, Lambing C, Roitinger E et al. 2012. Inter-homolog crossing-over and synapsis in Arabidopsis meiosis are dependent on the chromosome axis protein AtASY3. PLOS Genet 8:e1002507
    [Google Scholar]
  89. 89.
    Woltering D, Baumgartner B, Bagchi S, Larkin B, Loidl J et al. 2000. Meiotic segregation, synapsis, and recombination checkpoint functions require physical interaction between the chromosomal proteins Red1p and Hop1p. Mol. Cell. Biol. 20:6646–58
    [Google Scholar]
  90. 90.
    Schalbetter SA, Fudenberg G, Baxter J, Pollard KS, Neale MJ. 2019. Principles of meiotic chromosome assembly revealed in S. cerevisiae. Nat. Commun. 10:4795
    [Google Scholar]
  91. 91.
    Alavattam KG, Maezawa S, Sakashita A, Khoury H, Barski A et al. 2019. Attenuated chromatin compartmentalization in meiosis and its maturation in sperm development. Nat. Struct. Mol. Biol. 26:175–84
    [Google Scholar]
  92. 92.
    Patel L, Kang R, Rosenberg SC, Qiu Y, Raviram R et al. 2019. Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase. Nat. Struct. Mol. Biol. 26:164–74
    [Google Scholar]
  93. 93.
    Wang Y, Wang H, Zhang Y, Du Z, Si W et al. 2019. Reprogramming of meiotic chromatin architecture during spermatogenesis. Mol. Cell 73:547–61.e6
    [Google Scholar]
  94. 94.
    Sun X, Huang L, Markowitz TE, Blitzblau HG, Chen D et al. 2015. Transcription dynamically patterns the meiotic chromosome-axis interface. eLife 4:e07424
    [Google Scholar]
  95. 95.
    Muller H, Scolari VF, Agier N, Piazza A, Thierry A et al. 2018. Characterizing meiotic chromosomes' structure and pairing using a designer sequence optimized for Hi-C. Mol. Syst. Biol. 14:e8293
    [Google Scholar]
  96. 96.
    Fujiwara Y, Horisawa-Takada Y, Inoue E, Tani N, Shibuya H et al. 2020. Meiotic cohesins mediate initial loading of HORMAD1 to the chromosomes and coordinate SC formation during meiotic prophase. PLOS Genet 16:e1009048
    [Google Scholar]
  97. 97.
    Kim Y, Rosenberg SC, Kugel CL, Kostow N, Rog O et al. 2014. The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins. Dev. Cell 31:487–502
    [Google Scholar]
  98. 98.
    Severson AF, Ling L, van Zuylen V, Meyer BJ. 2009. The axial element protein HTP-3 promotes cohesin loading and meiotic axis assembly in C. elegans to implement the meiotic program of chromosome segregation. Genes Dev 23:1763–78
    [Google Scholar]
  99. 99.
    Kohler S, Wojcik M, Xu K, Dernburg AF. 2017. Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact Caenorhabditis elegans tissue. PNAS 114:E4734–43
    [Google Scholar]
  100. 100.
    Daniel K, Lange J, Hached K, Fu J, Anastassiadis K et al. 2011. Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1. Nat. Cell. Biol. 13:599–610
    [Google Scholar]
  101. 101.
    Shin YH, Choi Y, Erdin SU, Yatsenko SA, Kloc M et al. 2010. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis. PLOS Genet 6:e1001190
    [Google Scholar]
  102. 102.
    Hollingsworth NM, Byers B. 1989. HOP1: a yeast meiotic pairing gene. Genetics 121:445–62
    [Google Scholar]
  103. 103.
    Panizza S, Mendoza MA, Berlinger M, Huang L, Nicolas A et al. 2011. Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination. Cell 146:372–83
    [Google Scholar]
  104. 104.
    Goodyer W, Kaitna S, Couteau F, Ward JD, Boulton SJ, Zetka M. 2008. HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis. Dev. Cell 14:263–74
    [Google Scholar]
  105. 105.
    Rousova D, Nivsarkar V, Altmannova V, Funk SK, Raina VB et al. 2020. Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation. bioRxiv 2020.07.30.228908 https://doi.org/10.1101/2020.07.30.228908
    [Crossref]
  106. 106.
    Stanzione M, Baumann M, Papanikos F, Dereli I, Lange J et al. 2016. Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice. Nat. Cell. Biol. 18:1208–20
    [Google Scholar]
  107. 107.
    Kariyazono R, Oda A, Yamada T, Ohta K 2019. Conserved HORMA domain–containing protein Hop1 stabilizes interaction between proteins of meiotic DNA break hotspots and chromosome axis. Nucleic Acids Res 47:10166–80
    [Google Scholar]
  108. 108.
    Claeys Bouuaert C, Pu S, Wang J, Oger C, Daccache D et al. 2021. DNA-driven condensation assembles the meiotic DNA break machinery. Nature 592:144–49
    [Google Scholar]
  109. 109.
    Li J, Hooker GW, Roeder GS. 2006. Saccharomyces cerevisiae Mer2, Mei4 and Rec114 form a complex required for meiotic double-strand break formation. Genetics 173:1969–81
    [Google Scholar]
  110. 110.
    Sasanuma H, Murakami H, Fukuda T, Shibata T, Nicolas A, Ohta K 2007. Meiotic association between Spo11 regulated by Rec102, Rec104 and Rec114. Nucleic Acids Res 35:1119–33
    [Google Scholar]
  111. 111.
    Subramanian VV, Hochwagen A. 2014. The meiotic checkpoint network: step-by-step through meiotic prophase. Cold Spring Harb. Perspect. Biol. 6:a016675
    [Google Scholar]
  112. 112.
    Niu H, Wan L, Baumgartner B, Schaefer D, Loidl J, Hollingsworth NM 2005. Partner choice during meiosis is regulated by Hop1-promoted dimerization of Mek1. Mol. Biol. Cell 16:5804–18
    [Google Scholar]
  113. 113.
    Latypov V, Rothenberg M, Lorenz A, Octobre G, Csutak O et al. 2010. Roles of Hop1 and Mek1 in meiotic chromosome pairing and recombination partner choice in Schizosaccharomyces pombe. Mol. Cell. Biol. 30:1570–81
    [Google Scholar]
  114. 114.
    Sanchez-Moran E, Santos JL, Jones GH, Franklin FC. 2007. ASY1 mediates AtDMC1-dependent interhomolog recombination during meiosis in Arabidopsis. Genes Dev 21:2220–33
    [Google Scholar]
  115. 115.
    Chuang CN, Cheng YH, Wang TF. 2012. Mek1 stabilizes Hop1-Thr318 phosphorylation to promote interhomolog recombination and checkpoint responses during yeast meiosis. Nucleic Acids Res 40:11416–27
    [Google Scholar]
  116. 116.
    Subramanian VV, MacQueen AJ, Vader G, Shinohara M, Sanchez A et al. 2016. Chromosome synapsis alleviates Mek1-dependent suppression of meiotic DNA repair. PLOS Biol 14:e1002369
    [Google Scholar]
  117. 117.
    Carballo JA, Johnson AL, Sedgwick SG, Cha RS. 2008. Phosphorylation of the axial element protein Hop1 by Mec1/Tel1 ensures meiotic interhomolog recombination. Cell 132:758–70
    [Google Scholar]
  118. 118.
    Niu H, Li X, Job E, Park C, Moazed D et al. 2007. Mek1 kinase is regulated to suppress double-strand break repair between sister chromatids during budding yeast meiosis. Mol. Cell. Biol. 27:5456–67
    [Google Scholar]
  119. 119.
    Niu H, Wan L, Busygina V, Kwon Y, Allen JA et al. 2009. Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation. Mol. Cell 36:393–404
    [Google Scholar]
  120. 120.
    Govin J, Dorsey J, Gaucher J, Rousseaux S, Khochbin S, Berger SL 2010. Systematic screen reveals new functional dynamics of histones H3 and H4 during gametogenesis. Genes Dev 24:1772–86
    [Google Scholar]
  121. 121.
    Yang C, Hu B, Portheine SM, Chuenban P, Schnittger A 2020. State changes of the HORMA protein ASY1 are mediated by an interplay between its closure motif and PCH2. Nucleic Acids Res 48:11521–35
    [Google Scholar]
  122. 122.
    Raina VB, Vader G 2020. Homeostatic control of meiotic prophase checkpoint function by Pch2 and Hop1. Curr. Biol. 30:4413–24.e5
    [Google Scholar]
  123. 123.
    Miao C, Tang D, Zhang H, Wang M, Li Y et al. 2013. CENTRAL REGION COMPONENT1, a novel synaptonemal complex component, is essential for meiotic recombination initiation in rice. Plant Cell 25:2998–3009
    [Google Scholar]
  124. 124.
    Herruzo E, Lago-Maciel A, Baztán S, Santos B, Carballo JA et al. 2021. Pch2 orchestrates the meiotic recombination checkpoint from the cytoplasm. PLOS Genet. 17:e1009560
    [Google Scholar]
  125. 125.
    Li XC, Schimenti JC. 2007. Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis. PLOS Genet 3:e130
    [Google Scholar]
  126. 126.
    Loidl J. 2016. Conservation and variability of meiosis across the eukaryotes. Annu. Rev. Genet. 50:293–316
    [Google Scholar]
  127. 127.
    Cahoon CK, Hawley RS. 2016. Regulating the construction and demolition of the synaptonemal complex. Nat. Struct. Mol. Biol. 23:369–77
    [Google Scholar]
  128. 128.
    Vader G. 2015. Pch2TRIP13: controlling cell division through regulation of HORMA domains. Chromosoma 124:333–39
    [Google Scholar]
  129. 129.
    Lambing C, Osman K, Nuntasoontorn K, West A, Higgins JD et al. 2015. Arabidopsis PCH2 mediates meiotic chromosome remodeling and maturation of crossovers. PLOS Genet 11:e1005372
    [Google Scholar]
  130. 130.
    Giacopazzi S, Vong D, Devigne A, Bhalla N 2020. PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions. PLOS Genet 16:e1008904
    [Google Scholar]
  131. 131.
    Ji J, Tang D, Shen Y, Xue Z, Wang H et al. 2016. P31comet, a member of the synaptonemal complex, participates in meiotic DSB formation in rice. PNAS 113:10577–82
    [Google Scholar]
  132. 132.
    Balboni M, Yang C, Komaki S, Brun J, Schnittger A. 2020. COMET functions as a PCH2 cofactor in regulating the HORMA domain protein ASY1. Curr. Biol. 30:4113–27.e6
    [Google Scholar]
  133. 133.
    van Hooff JJ, Tromer E, van Wijk LM, Snel B, Kops GJ 2017. Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics. EMBO Rep 18:1559–71
    [Google Scholar]
  134. 134.
    Chen C, Jomaa A, Ortega J, Alani EE. 2014. Pch2 is a hexameric ring ATPase that remodels the chromosome axis protein Hop1. PNAS 111:E44–53
    [Google Scholar]
  135. 135.
    Villar-Fernandez MA, Cardoso da Silva R, Firlej M, Pan D, Weir E et al. 2020. Biochemical and functional characterization of a meiosis-specific Pch2/ORC AAA+ assembly. Life Sci. Alliance 3:e201900630
    [Google Scholar]
  136. 136.
    Nelson JR, Lawrence CW, Hinkle DC 1996. Deoxycytidyl transferase activity of yeast REV1 protein. Nature 382:729–31
    [Google Scholar]
  137. 137.
    Nelson JR, Lawrence CW, Hinkle DC. 1996. Thymine-thymine dimer bypass by yeast DNA polymerase ζ. Science 272:1646–49
    [Google Scholar]
  138. 138.
    Johnson RE, Prakash L, Prakash S. 2012. Pol31 and Pol32 subunits of yeast DNA polymerase δ are also essential subunits of DNA polymerase ζ. PNAS 109:12455–60
    [Google Scholar]
  139. 139.
    Murakumo Y, Roth T, Ishii H, Rasio D, Numata S et al. 2000. A human REV7 homolog that interacts with the polymerase ζ catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2. J. Biol. Chem. 275:4391–97
    [Google Scholar]
  140. 140.
    Sale JE. 2013. Translesion DNA synthesis and mutagenesis in eukaryotes. Cold Spring Harb. Perspect. Biol. 5:a012708
    [Google Scholar]
  141. 141.
    Hara K, Shimizu T, Unzai S, Akashi S, Sato M, Hashimoto H. 2009. Purification, crystallization and initial X-ray diffraction study of human REV7 in complex with a REV3 fragment. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 65:1302–5
    [Google Scholar]
  142. 142.
    Hara K, Hashimoto H, Murakumo Y, Kobayashi S, Kogame T et al. 2010. Crystal structure of human REV7 in complex with a human REV3 fragment and structural implication of the interaction between DNA polymerase ζ and REV1. J. Biol. Chem. 285:12299–307
    [Google Scholar]
  143. 143.
    Tomida J, Takata K, Lange SS, Schibler AC, Yousefzadeh MJ et al. 2015. REV7 is essential for DNA damage tolerance via two REV3L binding sites in mammalian DNA polymerase ζ. Nucleic Acids Res 43:1000–11
    [Google Scholar]
  144. 144.
    Rizzo AA, Vassel FM, Chatterjee N, D'Souza S, Li Y et al. 2018. Rev7 dimerization is important for assembly and function of the Rev1/Polζ translesion synthesis complex. PNAS 115:E8191–200
    [Google Scholar]
  145. 145.
    Malik R, Kopylov M, Gomez-Llorente Y, Jain R, Johnson RE et al. 2020. Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis. Nat. Struct. Mol. Biol. 27:913–24
    [Google Scholar]
  146. 146.
    Du Truong C, Craig TA, Cui G, Victoria Botuyan M, Serkasevich RA et al. 2021. Cryo-EM reveals conformational flexibility in apo DNA polymerase ζ. J. Biol. Chem. 297:100912
    [Google Scholar]
  147. 147.
    Wojtaszek J, Lee CJ, D'Souza S, Minesinger B, Kim H et al. 2012. Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion polymerase complex consisting of Rev1, heterodimeric polymerase (Pol) ζ, and Pol κ. J. Biol. Chem. 287:33836–46
    [Google Scholar]
  148. 148.
    Pustovalova Y, Bezsonova I, Korzhnev DM. 2012. The C-terminal domain of human Rev1 contains independent binding sites for DNA polymerase η and Rev7 subunit of polymerase ζ. FEBS Lett 586:3051–56
    [Google Scholar]
  149. 149.
    Pozhidaeva A, Pustovalova Y, D'Souza S, Bezsonova I, Walker GC, Korzhnev DM 2012. NMR structure and dynamics of the C-terminal domain from human Rev1 and its complex with Rev1 interacting region of DNA polymerase η. Biochemistry 51:5506–20
    [Google Scholar]
  150. 150.
    Ohashi E, Hanafusa T, Kamei K, Song I, Tomida J et al. 2009. Identification of a novel REV1-interacting motif necessary for DNA polymerase κ function. Genes Cells 14:101–11
    [Google Scholar]
  151. 151.
    Jain R, Aggarwal AK, Rechkoblit O. 2018. Eukaryotic DNA polymerases. Curr. Opin. Struct. Biol. 53:77–87
    [Google Scholar]
  152. 152.
    Prakash S, Johnson RE, Prakash L 2005. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu. Rev. Biochem. 74:317–53
    [Google Scholar]
  153. 153.
    Xu G, Chapman JR, Brandsma I, Yuan J, Mistrik M et al. 2015. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature 521:541–44
    [Google Scholar]
  154. 154.
    Noordermeer SM, Adam S, Setiaputra D, Barazas M, Pettitt SJ et al. 2018. The shieldin complex mediates 53BP1-dependent DNA repair. Nature 560:117–21
    [Google Scholar]
  155. 155.
    Mirman Z, Lottersberger F, Takai H, Kibe T, Gong Y et al. 2018. 53BP1-RIF1-shieldin counteracts DSB resection through CST- and Polα-dependent fill-in. Nature 560:112–16
    [Google Scholar]
  156. 156.
    Ghezraoui H, Oliveira C, Becker JR, Bilham K, Moralli D et al. 2018. 53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ. Nature 560:122–27
    [Google Scholar]
  157. 157.
    Barazas M, Annunziato S, Pettitt SJ, de Krijger I, Ghezraoui H et al. 2018. The CST complex mediates end protection at double-strand breaks and promotes PARP inhibitor sensitivity in BRCA1-deficient cells. Cell Rep 23:2107–18
    [Google Scholar]
  158. 158.
    Setiaputra D, Durocher D. 2019. Shieldin – the protector of DNA ends. EMBO Rep 20:e47560
    [Google Scholar]
  159. 159.
    Sarangi P, Clairmont CS, Galli LD, Moreau LA, D'Andrea AD. 2020. p31comet promotes homologous recombination by inactivating REV7 through the TRIP13 ATPase. PNAS 117:26795–803
    [Google Scholar]
  160. 160.
    Chen J, Fang G 2001. MAD2B is an inhibitor of the anaphase-promoting complex. Genes Dev 15:1765–70
    [Google Scholar]
  161. 161.
    Pfleger CM, Salic A, Lee E, Kirschner MW 2001. Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1. Genes Dev 15:1759–64
    [Google Scholar]
  162. 162.
    Listovsky T, Sale JE. 2013. Sequestration of CDH1 by MAD2L2 prevents premature APC/C activation prior to anaphase onset. J. Cell Biol. 203:87–100
    [Google Scholar]
  163. 163.
    Medendorp K, van Groningen JJ, Vreede L, Hetterschijt L, van den Hurk WH et al. 2009. The mitotic arrest deficient protein MAD2B interacts with the small GTPase RAN throughout the cell cycle. PLOS ONE 4:e7020
    [Google Scholar]
  164. 164.
    Wang X, Pernicone N, Pertz L, Hua D, Zhang T et al. 2019. REV7 has a dynamic adaptor region to accommodate small GTPase RAN/Shigella IpaB ligands, and its activity is regulated by the RanGTP/GDP switch. J. Biol. Chem. 294:15733–42
    [Google Scholar]
  165. 165.
    Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y et al. 2017. Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment-maintaining phosphoprotein (CAMP). J. Biol. Chem. 292:17658–67
    [Google Scholar]
  166. 166.
    Iwai H, Kim M, Yoshikawa Y, Ashida H, Ogawa M et al. 2007. A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling. Cell 130:611–23
    [Google Scholar]
  167. 167.
    Mizushima N. 2010. The role of the Atg1/ULK1 complex in autophagy regulation. Curr. Opin. Cell Biol. 22:132–39
    [Google Scholar]
  168. 168.
    Stephan JS, Yeh YY, Ramachandran V, Deminoff SJ, Herman PK. 2009. The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. PNAS 106:17049–54
    [Google Scholar]
  169. 169.
    Kamada Y, Yoshino K, Kondo C, Kawamata T, Oshiro N et al. 2010. Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol. Cell. Biol. 30:1049–58
    [Google Scholar]
  170. 170.
    Puente C, Hendrickson RC, Jiang X. 2016. Nutrient-regulated phosphorylation of ATG13 inhibits starvation-induced autophagy. J. Biol. Chem. 291:6026–35
    [Google Scholar]
  171. 171.
    Fujioka Y, Suzuki SW, Yamamoto H, Kondo-Kakuta C, Kimura Y et al. 2014. Structural basis of starvation-induced assembly of the autophagy initiation complex. Nat. Struct. Mol. Biol. 21:513–21
    [Google Scholar]
  172. 172.
    Yamamoto H, Fujioka Y, Suzuki SW, Noshiro D, Suzuki H et al. 2016. The intrinsically disordered protein Atg13 mediates supramolecular assembly of autophagy initiation complexes. Dev. Cell 38:86–99
    [Google Scholar]
  173. 173.
    Shi X, Yokom AL, Wang C, Young LN, Youle RJ, Hurley JH 2020. ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer. J. Cell Biol. 219:e201911047
    [Google Scholar]
  174. 174.
    Scott SV, Nice DC 3rd, Nau JJ, Weisman LS, Kamada Y et al. 2000. Apg13p and Vac8p are part of a complex of phosphoproteins that are required for cytoplasm to vacuole targeting. J. Biol. Chem. 275:25840–49
    [Google Scholar]
  175. 175.
    Hollenstein DM, Gomez-Sanchez R, Ciftci A, Kriegenburg F, Mari M et al. 2019. Vac8 spatially confines autophagosome formation at the vacuole in S. cerevisiae. J. Cell Sci. 132:jcs235002
    [Google Scholar]
  176. 176.
    Fujioka Y, Alam JM, Noshiro D, Mouri K, Ando T et al. 2020. Phase separation organizes the site of autophagosome formation. Nature 578:301–5
    [Google Scholar]
  177. 177.
    Memisoglu G, Eapen VV, Yang Y, Klionsky DJ, Haber JE 2019. PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex. PNAS 116:1613–20
    [Google Scholar]
  178. 178.
    Park JM, Jung CH, Seo M, Otto NM, Grunwald D et al. 2016. The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy 12:547–64
    [Google Scholar]
  179. 179.
    Yamamoto H, Kakuta S, Watanabe TM, Kitamura A, Sekito T et al. 2012. Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J. Cell Biol. 198:219–33
    [Google Scholar]
  180. 180.
    Wallot-Hieke N, Verma N, Schlutermann D, Berleth N, Deitersen J et al. 2018. Systematic analysis of ATG13 domain requirements for autophagy induction. Autophagy 14:743–63
    [Google Scholar]
  181. 181.
    Suzuki SW, Yamamoto H, Oikawa Y, Kondo-Kakuta C, Kimura Y et al. 2015. Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation. PNAS 112:3350–55
    [Google Scholar]
  182. 182.
    Rao Y, Perna MG, Hofmann B, Beier V, Wollert T. 2016. The Atg1–kinase complex tethers Atg9-vesicles to initiate autophagy. Nat. Commun. 7:10338
    [Google Scholar]
  183. 183.
    Gordon DJ, Resio B, Pellman D 2012. Causes and consequences of aneuploidy in cancer. Nat. Rev. Genet. 13:189–203
    [Google Scholar]
  184. 184.
    Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordon-Cardo C et al. 2007. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11:9–23
    [Google Scholar]
  185. 185.
    Chen YT, Venditti CA, Theiler G, Stevenson BJ, Iseli C et al. 2005. Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein. Cancer Immun 5:9
    [Google Scholar]
  186. 186.
    Aung PP, Oue N, Mitani Y, Nakayama H, Yoshida K et al. 2006. Systematic search for gastric cancer-specific genes based on SAGE data: Melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer. Oncogene 25:2546–57
    [Google Scholar]
  187. 187.
    Nichols BA, Oswald NW, McMillan EA, McGlynn K, Yan J et al. 2018. HORMAD1 is a negative prognostic indicator in lung adenocarcinoma and specifies resistance to oxidative and genotoxic stress. Cancer Res 78:6196–208
    [Google Scholar]
  188. 188.
    Gao Y, Kardos J, Yang Y, Tamir TY, Mutter-Rottmayer E et al. 2018. The cancer/testes (CT) antigen HORMAD1 promotes homologous recombinational DNA repair and radioresistance in lung adenocarcinoma cells. Sci. Rep. 8:15304
    [Google Scholar]
  189. 189.
    Adelaide J, Finetti P, Bekhouche I, Repellini L, Geneix J et al. 2007. Integrated profiling of basal and luminal breast cancers. Cancer Res 67:11565–75
    [Google Scholar]
  190. 190.
    Yao J, Caballero OL, Yung WK, Weinstein JN, Riggins GJ et al. 2014. Tumor subtype-specific cancer—testis antigens as potential biomarkers and immunotherapeutic targets for cancers. Cancer Immunol. Res. 2:371–79
    [Google Scholar]
  191. 191.
    Watkins J, Weekes D, Shah V, Gazinska P, Joshi S et al. 2015. Genomic complexity profiling reveals that HORMAD1 overexpression contributes to homologous recombination deficiency in triple-negative breast cancers. Cancer Discov 5:488–505
    [Google Scholar]
  192. 192.
    Holm K, Staaf J, Lauss M, Aine M, Lindgren D et al. 2016. An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells. Breast Cancer Res 18:27
    [Google Scholar]
  193. 193.
    Wang X, Tan Y, Cao X, Kim JA, Chen T et al. 2018. Epigenetic activation of HORMAD1 in basal-like breast cancer: role in Rucaparib sensitivity. Oncotarget 9:30115–27
    [Google Scholar]
  194. 194.
    Lin Q, Hou S, Guan F, Lin C 2018. HORMAD2 methylation-mediated epigenetic regulation of gene expression in thyroid cancer. J. Cell Mol. Med. 22:4640–52
    [Google Scholar]
  195. 195.
    Liu M, Chen J, Hu L, Shi X, Zhou Z et al. 2012. HORMAD2/CT46.2, a novel cancer/testis gene, is ectopically expressed in lung cancer tissues. Mol. Hum. Reprod. 18:599–604
    [Google Scholar]
  196. 196.
    Liu K, Wang Y, Zhu Q, Li P, Chen J et al. 2020. Aberrantly expressed HORMAD1 disrupts nuclear localization of MCM8–MCM9 complex and compromises DNA mismatch repair in cancer cells. Cell Death Dis 11:519
    [Google Scholar]
  197. 197.
    Boersma V, Moatti N, Segura-Bayona S, Peuscher MH, van der Torre J et al. 2015. MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5′ end resection. Nature 521:537–40
    [Google Scholar]
  198. 198.
    Tomida J, Takata KI, Bhetawal S, Person MD, Chao HP et al. 2018. FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells. EMBO J 37:e99543
    [Google Scholar]
  199. 199.
    Vassel FM, Bian K, Walker GC, Hemann MT. 2020. Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer. PNAS 117:28922–24
    [Google Scholar]
  200. 200.
    Niimi K, Murakumo Y, Watanabe N, Kato T, Mii S et al. 2014. Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells. Cancer Sci 105:545–52
    [Google Scholar]
  201. 201.
    Chatterjee N, Whitman MA, Harris CA, Min SM, Jonas O et al. 2020. REV1 inhibitor JH-RE-06 enhances tumor cell response to chemotherapy by triggering senescence hallmarks. PNAS 117:28918–21
    [Google Scholar]
  202. 202.
    Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R et al. 2004. Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. PNAS 101:9309–14
    [Google Scholar]
  203. 203.
    Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z. 2006. A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat. Genet. 38:1043–48
    [Google Scholar]
  204. 204.
    Dazhi W, Mengxi Z, Fufeng C, Meixing Y. 2017. Elevated expression of thyroid hormone receptor-interacting protein 13 drives tumorigenesis and affects clinical outcome. Biomark. Med. 11:19–31
    [Google Scholar]
  205. 205.
    Ju L, Li X, Shao J, Lu R, Wang Y, Bian Z 2018. Upregulation of thyroid hormone receptor interactor 13 is associated with human hepatocellular carcinoma. Oncol. Rep. 40:3794–802
    [Google Scholar]
  206. 206.
    Yao J, Zhang X, Li J, Zhao D, Gao B et al. 2018. Silencing TRIP13 inhibits cell growth and metastasis of hepatocellular carcinoma by activating of TGF-β1/smad3. Cancer Cell Int 18:208
    [Google Scholar]
  207. 207.
    Wang D, Liu J, Liu S, Li W. 2020. Identification of crucial genes associated with immune cell infiltration in hepatocellular carcinoma by weighted gene co-expression network analysis. Front. Genet. 11:342
    [Google Scholar]
  208. 208.
    Martin KJ, Patrick DR, Bissell MJ, Fournier MV. 2008. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets. PLOS ONE 3:e2994
    [Google Scholar]
  209. 209.
    Maurizio E, Wisniewski JR, Ciani Y, Amato A, Arnoldo L et al. 2016. Translating proteomic into functional data: An high mobility group A1 (HMGA1) proteomic signature has prognostic value in breast cancer. Mol. Cell Proteom. 15:109–23
    [Google Scholar]
  210. 210.
    Nieto-Jimenez C, Alcaraz-Sanabria A, Paez R, Perez-Pena J, Corrales-Sanchez V et al. 2017. DNA-damage related genes and clinical outcome in hormone receptor positive breast cancer. Oncotarget 8:62834–41
    [Google Scholar]
  211. 211.
    Zhang Y, Xue Q, Pan G, Meng QH, Tuo X et al. 2017. Integrated analysis of genome-wide copy number alterations and gene expression profiling of lung cancer in Xuanwei, China. PLOS ONE 12:e0169098
    [Google Scholar]
  212. 212.
    Li W, Zhang G, Li X, Wang X, Li Q et al. 2018. Thyroid hormone receptor interactor 13 (TRIP13) overexpression associated with tumor progression and poor prognosis in lung adenocarcinoma. Biochem. Biophys. Res. Commun. 499:416–24
    [Google Scholar]
  213. 213.
    Zhang Q, Dong Y, Hao S, Tong Y, Luo Q, Aerxiding P. 2019. The oncogenic role of TRIP13 in regulating proliferation, invasion, and cell cycle checkpoint in NSCLC cells. Int. J. Clin. Exp. Pathol. 12:3357–66
    [Google Scholar]
  214. 214.
    Abdul Aziz NA, Mokhtar NM, Harun R, Mollah MM, Mohamed Rose I et al. 2016. A 19-gene expression signature as a predictor of survival in colorectal cancer. BMC Med. Genom. 9:58
    [Google Scholar]
  215. 215.
    Kurita K, Maeda M, Mansour MA, Kokuryo T, Uehara K et al. 2016. TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion. Oncol. Lett. 12:5240–46
    [Google Scholar]
  216. 216.
    Sheng N, Yan L, Wu K, You W, Gong J et al. 2018. TRIP13 promotes tumor growth and is associated with poor prognosis in colorectal cancer. Cell Death Dis 9:402
    [Google Scholar]
  217. 217.
    Larkin SE, Holmes S, Cree IA, Walker T, Basketter V et al. 2012. Identification of markers of prostate cancer progression using candidate gene expression. Br. J. Cancer 106:157–65
    [Google Scholar]
  218. 218.
    van Kester MS, Borg MK, Zoutman WH, Out-Luiting JJ, Jansen PM et al. 2012. A meta-analysis of gene expression data identifies a molecular signature characteristic for tumor-stage mycosis fungoides. J. Invest. Dermatol. 132:2050–59
    [Google Scholar]
  219. 219.
    Tao Y, Yang G, Yang H, Song D, Hu L et al. 2017. TRIP13 impairs mitotic checkpoint surveillance and is associated with poor prognosis in multiple myeloma. Oncotarget 8:26718–31
    [Google Scholar]
  220. 220.
    Zhou K, Zhang W, Zhang Q, Gui R, Zhao H et al. 2017. Loss of thyroid hormone receptor interactor 13 inhibits cell proliferation and survival in human chronic lymphocytic leukemia. Oncotarget 8:25469–81
    [Google Scholar]
  221. 221.
    Dong L, Ding H, Li Y, Xue D, Li Z et al. 2019. TRIP13 is a predictor for poor prognosis and regulates cell proliferation, migration and invasion in prostate cancer. Int. J. Biol. Macromol. 121:200–6
    [Google Scholar]
  222. 222.
    Liu M, Qiu YL, Jin T, Zhou Y, Mao ZY, Zhang YJ 2018. Meta-analysis of microarray datasets identify several chromosome segregation-related cancer/testis genes potentially contributing to anaplastic thyroid carcinoma. PeerJ 6:e5822
    [Google Scholar]
  223. 223.
    Yan X, Guo ZX, Liu XP, Feng YJ, Zhao YJ et al. 2019. Four novel biomarkers for bladder cancer identified by weighted gene coexpression network analysis. J. Cell Physiol. 234:19073–87
    [Google Scholar]
  224. 224.
    Di S, Li M, Ma Z, Guo K, Li X, Yan X 2019. TRIP13 upregulation is correlated with poor prognosis and tumor progression in esophageal squamous cell carcinoma. Pathol. Res. Pract. 215:152415
    [Google Scholar]
  225. 225.
    Gao Y, Liu S, Guo Q, Zhang S, Zhao Y et al. 2019. Increased expression of TRIP13 drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway. Int. J. Biol. Sci. 15:1488–99
    [Google Scholar]
  226. 226.
    Lu S, Guo M, Fan Z, Chen Y, Shi X et al. 2019. Elevated TRIP13 drives cell proliferation and drug resistance in bladder cancer. Am. J. Transl. Res. 11:4397–410
    [Google Scholar]
  227. 227.
    Niu L, Gao Z, Cui Y, Yang X, Li H 2019. Thyroid receptor-interacting protein 13 is correlated with progression and poor prognosis in bladder cancer. Med. Sci. Monit. 25:6660–68
    [Google Scholar]
  228. 228.
    Yu L, Xiao Y, Zhou X, Wang J, Chen S et al. 2019. TRIP13 interference inhibits the proliferation and metastasis of thyroid cancer cells through regulating TTC5/p53 pathway and epithelial-mesenchymal transition related genes expression. Biomed. Pharmacother. 120:109508
    [Google Scholar]
  229. 229.
    Wang Y, Huang J, Li B, Xue H, Tricot G et al. 2020. A small-molecule inhibitor targeting TRIP13 suppresses multiple myeloma progression. Cancer Res 80:536–48
    [Google Scholar]
  230. 230.
    Banerjee R, Russo N, Liu M, Basrur V, Bellile E et al. 2014. TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer. Nat. Commun. 5:4527
    [Google Scholar]
  231. 231.
    Yost S, de Wolf B, Hanks S, Zachariou A, Marcozzi C et al. 2017. Biallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation. Nat. Genet. 49:1148–51
    [Google Scholar]
  232. 232.
    Xie W, Yang X, Xu M, Jiang T 2012. Structural insights into the assembly of human translesion polymerase complexes. Protein Cell 3:864–74
    [Google Scholar]
  233. 233.
    Dev H, Chiang TW, Lescale C, de Krijger I, Martin AG et al. 2018. Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Nat. Cell. Biol. 20:954–65
    [Google Scholar]
  234. 234.
    Marks DH, Thomas R, Chin Y, Shah R, Khoo C, Benezra R. 2017. Mad2 overexpression uncovers a critical role for TRIP13 in mitotic exit. Cell Rep 19:1832–45
    [Google Scholar]
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