1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Biochemistry
  4. Volume 89, 2020
  5. Article

Annual Review of Biochemistry

Volume 89, 2020

Checkpoint Responses to DNA Double-Strand Breaks

Abstract

Cells confront DNA damage in every cell cycle. Among the most deleterious types of DNA damage are DNA double-strand breaks (DSBs), which can cause cell lethality if unrepaired or cancers if improperly repaired. In response to DNA DSBs, cells activate a complex DNA damage checkpoint (DDC) response that arrests the cell cycle, reprograms gene expression, and mobilizes DNA repair factors to prevent the inheritance of unrepaired and broken chromosomes. Here we examine the DDC, induced by DNA DSBs, in the budding yeast model system and in mammals.

Keyword(s): cell cycle, checkpoint, DNA double-strand break, DNA repair, kinases
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-011520-104722
2020-06-20
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/biochem/89/1/annurev-biochem-011520-104722.html?itemId=/content/journals/10.1146/annurev-biochem-011520-104722&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Hoeijmakers JH. 2009. DNA damage, aging, and cancer. N. Engl. J. Med. 361:1475–85
     [Google Scholar]
  2. 2. 
    Branzei D, Foiani M. 2005. The DNA damage response during DNA replication. Curr. Opin. Cell Biol. 17:568–75
     [Google Scholar]
  3. 3. 
    Scharer OD. 2013. Nucleotide excision repair in eukaryotes. Cold Spring Harb. Perspect. Biol. 5:a012609
     [Google Scholar]
  4. 4. 
    Krokan HE, Bjoras M. 2013. Base excision repair. Cold Spring Harb. Perspect. Biol. 5:a012583
     [Google Scholar]
  5. 5. 
    Alexander JL, Orr-Weaver TL. 2016. Replication fork instability and the consequences of fork collisions from rereplication. Genes Dev 30:2241–52
     [Google Scholar]
  6. 6. 
    Sonoda E, Sasaki MS, Buerstedde JM, Bezzubova O, Shinohara A et al. 1998. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J 17:598–608
     [Google Scholar]
  7. 7. 
    Vilenchik MM, Knudson AG. 2003. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. PNAS 100:12871–76
     [Google Scholar]
  8. 8. 
    Haber JE. 2014. Genome Stability: DNA Repair and Recombination New York: GS/Garland Science, Taylor & Francis Group
  9. 9. 
    Jacquier A, Dujon B. 1985. An intron-encoded protein is active in a gene conversion process that spreads an intron into a mitochondrial gene. Cell 41:383–94
     [Google Scholar]
  10. 10. 
    Lee CS, Haber JE. 2015. Mating-type gene switching in Saccharomyces cerevisiae. Microbiol. Spectr 3:MDNA3–0013–2014
     [Google Scholar]
  11. 11. 
    Haber JE. 2016. A life investigating pathways that repair broken chromosomes. Annu. Rev. Genet. 50:1–28
     [Google Scholar]
  12. 12. 
    Jasin M, Rothstein R. 2013. Repair of strand breaks by homologous recombination. Cold Spring Harb. Perspect. Biol. 5:a012740
     [Google Scholar]
  13. 13. 
    Kaplun L, Ivantsiv Y, Kornitzer D, Raveh D 2000. Functions of the DNA damage response pathway target Ho endonuclease of yeast for degradation via the ubiquitin-26S proteasome system. PNAS 97:10077–82
     [Google Scholar]
  14. 14. 
    DiCarlo JE, Norville JE, Mali P, Rios X, Aach J, Church GM 2013. Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems. Nucleic Acids Res 41:4336–43
     [Google Scholar]
  15. 15. 
    Caron P, Choudjaye J, Clouaire T, Bugler B, Daburon V et al. 2015. Non-redundant functions of ATM and DNA-PKcs in response to DNA double-strand breaks. Cell Rep 13:1598–609
     [Google Scholar]
  16. 16. 
    Aymard F, Bugler B, Schmidt CK, Guillou E, Caron P et al. 2014. Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks. Nat. Struct. Mol. Biol. 21:366–74
     [Google Scholar]
  17. 17. 
    Jasin M, Haber JE. 2016. The democratization of gene editing: insights from site-specific cleavage and double-strand break repair. DNA Repair 44:6–16
     [Google Scholar]
  18. 18. 
    van den Berg J, Manjón AG, Kielbassa K, Feringa FM, Freire R, Medema RH 2018. A limited number of double-strand DNA breaks is sufficient to delay cell cycle progression. Nucleic Acids Res 46:10132–44
     [Google Scholar]
  19. 19. 
    Ceccaldi R, Rondinelli B, D'Andrea AD 2016. Repair pathway choices and consequences at the double-strand break. Trends Cell Biol 26:52–64
     [Google Scholar]
  20. 20. 
    Kakarougkas A, Jeggo PA. 2014. DNA DSB repair pathway choice: an orchestrated handover mechanism. Br. J. Radiol. 87:20130685
     [Google Scholar]
  21. 21. 
    Hannan MA, Miller DR, Nasim A 1976. Changes in uv-inactivation kinetics and division delay in Schizosaccharomyces pombe strains during different growth phases. Radiat. Res. 68:469–79
     [Google Scholar]
  22. 22. 
    Painter RB, Young BR. 1980. Radiosensitivity in ataxia-telangiectasia: a new explanation. PNAS 77:7315–17
     [Google Scholar]
  23. 23. 
    Weinert TA, Hartwell LH. 1988. The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 241:317–22
     [Google Scholar]
  24. 24. 
    Murray JM, Carr AM. 2018. Integrating DNA damage repair with the cell cycle. Curr. Opin. Cell Biol. 52:120–25
     [Google Scholar]
  25. 25. 
    Siede W, Friedberg AS, Dianova I, Friedberg EC 1994. Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents. Genetics 138:271–81
     [Google Scholar]
  26. 26. 
    Gerald JN, Benjamin JM, Kron SJ 2002. Robust G1 checkpoint arrest in budding yeast: dependence on DNA damage signaling and repair. J. Cell Sci. 115:1749–57
     [Google Scholar]
  27. 27. 
    Paulovich AG, Hartwell LH. 1995. A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell 82:841–47
     [Google Scholar]
  28. 28. 
    Vaze MB, Pellicioli A, Lee SE, Ira G, Liberi G et al. 2002. Recovery from checkpoint-mediated arrest after repair of a double-strand break requires Srs2 helicase. Mol. Cell 10:373–85
     [Google Scholar]
  29. 29. 
    Harrison JC, Haber JE. 2006. Surviving the breakup: the DNA damage checkpoint. Annu. Rev. Genet. 40:209–35
     [Google Scholar]
  30. 30. 
    Shaltiel IA, Krenning L, Bruinsma W, Medema RH 2015. The same, only different—DNA damage checkpoints and their reversal throughout the cell cycle. J. Cell Sci. 128:607–20
     [Google Scholar]
  31. 31. 
    Sandell LL, Zakian VA. 1993. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 75:729–39
     [Google Scholar]
  32. 32. 
    Harrigan JA, Belotserkovskaya R, Coates J, Dimitrova DS, Polo SE et al. 2011. Replication stress induces 53BP1-containing OPT domains in G1 cells. J. Cell Biol. 193:97–108
     [Google Scholar]
  33. 33. 
    Lukas C, Savic V, Bekker-Jensen S, Doil C, Neumann B et al. 2011. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress. Nat. Cell Biol. 13:243–53
     [Google Scholar]
  34. 34. 
    Feng W, Jasin M. 2017. BRCA2 suppresses replication stress-induced mitotic and G1 abnormalities through homologous recombination. Nat. Commun. 8:525
     [Google Scholar]
  35. 35. 
    Blackford AN, Jackson SP. 2017. ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response. Mol. Cell 66:801–17
     [Google Scholar]
  36. 36. 
    Kim ST, Lim DS, Canman CE, Kastan MB 1999. Substrate specificities and identification of putative substrates of ATM kinase family members. J. Biol. Chem. 274:37538–43
     [Google Scholar]
  37. 37. 
    O'Neill T, Dwyer AJ, Ziv Y, Chan DW, Lees-Miller SP et al. 2000. Utilization of oriented peptide libraries to identify substrate motifs selected by ATM. J. Biol. Chem. 275:22719–27
     [Google Scholar]
  38. 38. 
    Perry J, Kleckner N. 2003. The ATRs, ATMs, and TORs are giant HEAT repeat proteins. Cell 112:151–55
     [Google Scholar]
  39. 39. 
    Luzwick JW, Nam EA, Zhao R, Cortez D 2014. Mutation of serine 1333 in the ATR HEAT repeats creates a hyperactive kinase. PLOS ONE 9:e99397
     [Google Scholar]
  40. 40. 
    Bosotti R, Isacchi A, Sonnhammer EL 2000. FAT: a novel domain in PIK-related kinases. Trends Biochem. Sci. 25:225–27
     [Google Scholar]
  41. 41. 
    Bakkenist CJ, Kastan MB. 2003. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506
     [Google Scholar]
  42. 42. 
    Mordes DA, Glick GG, Zhao R, Cortez D 2008. TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev 22:1478–89
     [Google Scholar]
  43. 43. 
    Jiang X, Sun Y, Chen S, Roy K, Price BD 2006. The FATC domains of PIKK proteins are functionally equivalent and participate in the Tip60-dependent activation of DNA-PKcs and ATM. J. Biol. Chem. 281:15741–46
     [Google Scholar]
  44. 44. 
    Ogi H, Goto GH, Ghosh A, Zencir S, Henry E, Sugimoto K 2015. Requirement of the FATC domain of protein kinase Tel1 for localization to DNA ends and target protein recognition. Mol. Biol. Cell 26:3480–88
     [Google Scholar]
  45. 45. 
    Baretic D, Pollard HK, Fisher DI, Johnson CM, Santhanam B et al. 2017. Structures of closed and open conformations of dimeric human ATM. Sci. Adv. 3:e1700933
     [Google Scholar]
  46. 46. 
    Wang X, Chu H, Lv M, Zhang Z, Qiu S et al. 2016. Structure of the intact ATM/Tel1 kinase. Nat. Commun. 7:11655
     [Google Scholar]
  47. 47. 
    Wang X, Ran T, Zhang X, Xin J, Zhang Z et al. 2017. 3.9 Å structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP. Science 358:1206–9
     [Google Scholar]
  48. 48. 
    Ma W, Westmoreland J, Nakai W, Malkova A, Resnick MA 2011. Characterizing resection at random and unique chromosome double-strand breaks and telomere ends. Methods Mol. Biol. 745:15–31
     [Google Scholar]
  49. 49. 
    Kramer KM, Brock JA, Bloom K, Moore JK, Haber JE 1994. Two different types of double-strand breaks in Saccharomyces cerevisiae are repaired by similar RAD52-independent, nonhomologous recombination events. Mol. Cell. Biol. 14:1293–301
     [Google Scholar]
  50. 50. 
    Oh J, Al-Zain A, Cannavo E, Cejka P, Symington LS 2016. Xrs2 dependent and independent functions of the Mre11-Rad50 complex. Mol. Cell 64:405–15
     [Google Scholar]
  51. 51. 
    Andres SN, Williams RS. 2017. CtIP/Ctp1/Sae2, molecular form fit for function. DNA Repair 56:109–17
     [Google Scholar]
  52. 52. 
    Cassani C, Gobbini E, Vertemara J, Wang W, Marsella A et al. 2018. Structurally distinct Mre11 domains mediate MRX functions in resection, end-tethering and DNA damage resistance. Nucleic Acids Res 46:2990–3008
     [Google Scholar]
  53. 53. 
    Lisby M, Mortensen UH, Rothstein R 2003. Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre. Nat. Cell Biol. 5:572–77
     [Google Scholar]
  54. 54. 
    Waterman DP, Zhou F, Li K, Lee CS, Tsabar M et al. 2019. Live cell monitoring of double strand breaks in S. cerevisiae. PLOS Genet 15:e1008001
     [Google Scholar]
  55. 55. 
    Lobachev K, Vitriol E, Stemple J, Resnick MA, Bloom K 2004. Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex. Curr. Biol. 14:2107–12
     [Google Scholar]
  56. 56. 
    Mimitou EP, Symington LS. 2008. Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature 455:770–74
     [Google Scholar]
  57. 57. 
    Shim EY, Chung WH, Nicolette ML, Zhang Y, Davis M et al. 2010. Saccharomyces cerevisiae Mre11/Rad50/Xrs2 and Ku proteins regulate association of Exo1 and Dna2 with DNA breaks. EMBO J 29:3370–80
     [Google Scholar]
  58. 58. 
    Mimitou EP, Symington LS. 2010. Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2. EMBO J 29:3358–69
     [Google Scholar]
  59. 59. 
    Lisby M, Barlow JH, Burgess RC, Rothstein R 2004. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Cell 118:699–713
     [Google Scholar]
  60. 60. 
    Langerak P, Mejia-Ramirez E, Limbo O, Russell P 2011. Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks. PLOS Genet 7:e1002271
     [Google Scholar]
  61. 61. 
    Huertas P, Jackson SP. 2009. Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. J. Biol. Chem. 284:9558–65
     [Google Scholar]
  62. 62. 
    Ivanov EL, Sugawara N, White CI, Fabre F, Haber JE 1994. Mutations in XRS2 and RAD50 delay but do not prevent mating-type switching in Saccharomyces cerevisiae. Mol. Cell. Biol. 14:3414–25
     [Google Scholar]
  63. 63. 
    Tsubouchi H, Ogawa H. 1998. A novel mre11 mutation impairs processing of double-strand breaks of DNA during both mitosis and meiosis. Mol. Cell. Biol. 18:260–68
     [Google Scholar]
  64. 64. 
    Zhu Z, Chung WH, Shim EY, Lee SE, Ira G 2008. Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell 134:981–94
     [Google Scholar]
  65. 65. 
    Diede SJ, Gottschling DE. 2001. Exonuclease activity is required for sequence addition and Cdc13p loading at a de novo telomere. Curr. Biol. 11:1336–40
     [Google Scholar]
  66. 66. 
    Huertas P, Cortes-Ledesma F, Sartori AA, Aguilera A, Jackson SP 2008. CDK targets Sae2 to control DNA-end resection and homologous recombination. Nature 455:689–92
     [Google Scholar]
  67. 67. 
    Fishman-Lobell J, Haber JE. 1992. Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science 258:480–84
     [Google Scholar]
  68. 68. 
    Cruz-Garcia A, Lopez-Saavedra A, Huertas P 2014. BRCA1 accelerates CtIP-mediated DNA-end resection. Cell Rep 9:451–59
     [Google Scholar]
  69. 69. 
    Bhargava R, Onyango DO, Stark JM 2016. Regulation of single-strand annealing and its role in genome maintenance. Trends Genet 32:566–75
     [Google Scholar]
  70. 70. 
    Bae SH, Seo YS. 2000. Characterization of the enzymatic properties of the yeast dna2 helicase/endonuclease suggests a new model for Okazaki fragment processing. J. Biol. Chem. 275:38022–31
     [Google Scholar]
  71. 71. 
    Budd ME, Campbell JL. 1995. A yeast gene required for DNA replication encodes a protein with homology to DNA helicases. PNAS 92:7642–46
     [Google Scholar]
  72. 72. 
    Stewart JA, Campbell JL, Bambara RA 2010. Dna2 is a structure-specific nuclease, with affinity for 5′-flap intermediates. Nucleic Acids Res 38:920–30
     [Google Scholar]
  73. 73. 
    Lydeard JR, Lipkin-Moore Z, Jain S, Eapen VV, Haber JE 2010. Sgs1 and Exo1 redundantly inhibit break-induced replication and de novo telomere addition at broken chromosome ends. PLOS Genet 6:e1000973
     [Google Scholar]
  74. 74. 
    Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL et al. 2011. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev 25:350–62
     [Google Scholar]
  75. 75. 
    Soniat MM, Myler LR, Kuo H-C, Paull TT, Finkelstein IJ 2019. RPA phosphorylation inhibits DNA resection. Mol. Cell 75:145–53.e5
     [Google Scholar]
  76. 76. 
    Chen X, Niu H, Chung WH, Zhu Z, Papusha A et al. 2011. Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. Nat. Struct. Mol. Biol. 18:1015–19
     [Google Scholar]
  77. 77. 
    Clerici M, Mantiero D, Guerini I, Lucchini G, Longhese MP 2008. The Yku70-Yku80 complex contributes to regulate double-strand break processing and checkpoint activation during the cell cycle. EMBO Rep 9:810–18
     [Google Scholar]
  78. 78. 
    Nakada D, Matsumoto K, Sugimoto K 2003. ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism. Genes Dev 17:1957–62
     [Google Scholar]
  79. 79. 
    Kim JH, Grosbart M, Anand R, Wyman C, Cejka P, Petrini JHJ 2017. The Mre11-Nbs1 interface is essential for viability and tumor suppression. Cell Rep 18:496–507
     [Google Scholar]
  80. 80. 
    Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM et al. 2004. Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr. Biol. 14:1703–11
     [Google Scholar]
  81. 81. 
    Ira G, Pellicioli A, Balijja A, Wang X, Fiorani S et al. 2004. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 431:1011–17
     [Google Scholar]
  82. 82. 
    Bonilla CY, Melo JA, Toczyski DP 2008. Colocalization of sensors is sufficient to activate the DNA damage checkpoint in the absence of damage. Mol. Cell 30:267–76
     [Google Scholar]
  83. 83. 
    Mantiero D, Clerici M, Lucchini G, Longhese MP 2007. Dual role for Saccharomyces cerevisiae Tel1 in the checkpoint response to double-strand breaks. EMBO Rep 8:380–87
     [Google Scholar]
  84. 84. 
    Zou L, Elledge SJ. 2003. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300:1542–48
     [Google Scholar]
  85. 85. 
    Saldivar JC, Cortez D, Cimprich KA 2017. The essential kinase ATR: ensuring faithful duplication of a challenging genome. Nat. Rev. Mol. Cell Biol. 18:622–36
     [Google Scholar]
  86. 86. 
    Wanrooij PH, Burgers PM. 2015. Yet another job for Dna2: checkpoint activation. DNA Repair 32:17–23
     [Google Scholar]
  87. 87. 
    Mordes DA, Nam EA, Cortez D 2008. Dpb11 activates the Mec1-Ddc2 complex. PNAS 105:18730–34
     [Google Scholar]
  88. 88. 
    Navadgi-Patil VM, Burgers PM. 2008. Yeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase. J. Biol. Chem. 283:35853–59
     [Google Scholar]
  89. 89. 
    Kumar S, Burgers PM. 2013. Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery. Genes Dev 27:313–21
     [Google Scholar]
  90. 90. 
    Bass TE, Luzwick JW, Kavanaugh G, Carroll C, Dungrawala H et al. 2016. ETAA1 acts at stalled replication forks to maintain genome integrity. Nat. Cell Biol. 18:1185–95
     [Google Scholar]
  91. 91. 
    Haahr P, Hoffmann S, Tollenaere MA, Ho T, Toledo LI et al. 2016. Activation of the ATR kinase by the RPA-binding protein ETAA1. Nat. Cell Biol. 18:1196–207
     [Google Scholar]
  92. 92. 
    Lee YC, Zhou Q, Chen J, Yuan J 2016. RPA-binding protein ETAA1 is an ATR activator involved in DNA replication stress response. Curr. Biol. 26:3257–68
     [Google Scholar]
  93. 93. 
    Usui T, Ogawa H, Petrini JH 2001. A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol. Cell 7:1255–66
     [Google Scholar]
  94. 94. 
    Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM 1998. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273:5858–68
     [Google Scholar]
  95. 95. 
    Savic V, Yin B, Maas NL, Bredemeyer AL, Carpenter AC et al. 2009. Formation of dynamic γ-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin. Mol. Cell 34:298–310
     [Google Scholar]
  96. 96. 
    Solovjeva LV, Svetlova MP, Chagin VO, Tomilin NV 2007. Inhibition of transcription at radiation-induced nuclear foci of phosphorylated histone H2AX in mammalian cells. Chromosome Res 15:787–97
     [Google Scholar]
  97. 97. 
    Caron P, van der Linden J, van Attikum H 2019. Bon voyage: a transcriptional journey around DNA breaks. DNA Repair 82:102686
     [Google Scholar]
  98. 98. 
    Lee SE, Pellicioli A, Demeter J, Vaze MP, Gasch AP et al. 2000. Arrest, adaptation, and recovery following a chromosome double-strand break in Saccharomyces cerevisiae. Cold Spring Harb. Symp. Quant. Biol 65:303–14
     [Google Scholar]
  99. 99. 
    Manfrini N, Clerici M, Wery M, Colombo CV, Descrimes M et al. 2015. Resection is responsible for loss of transcription around a double-strand break in Saccharomyces cerevisiae. eLife 4:e08942
     [Google Scholar]
  100. 100. 
    Kim JA, Kruhlak M, Dotiwala F, Nussenzweig A, Haber JE 2007. Heterochromatin is refractory to γ-H2AX modification in yeast and mammals. J. Cell Biol. 178:209–18
     [Google Scholar]
  101. 101. 
    Lee CS, Lee K, Legube G, Haber JE 2014. Dynamics of yeast histone H2A and H2B phosphorylation in response to a double-strand break. Nat. Struct. Mol. Biol. 21:103–9
     [Google Scholar]
  102. 102. 
    Li J, Coic E, Lee K, Lee CS, Kim JA et al. 2012. Regulation of budding yeast mating-type switching donor preference by the FHA domain of Fkh1. PLOS Genet 8:e1002630
     [Google Scholar]
  103. 103. 
    Li K, Bronk G, Kondev J, Haber JE 2019. Yeast ATM and ATR use different mechanisms to spread histone H2A phosphorylation around a DNA double-strand break. bioRxiv https://doi.org/10.1101/2019.12.17.877266
    [Crossref]
  104. 104. 
    Dotiwala F, Haase J, Arbel-Eden A, Bloom K, Haber JE 2007. The yeast DNA damage checkpoint proteins control a cytoplasmic response to DNA damage. PNAS 104:11358–63
     [Google Scholar]
  105. 105. 
    Dotiwala F, Harrison JC, Jain S, Sugawara N, Haber JE 2010. Mad2 prolongs DNA damage checkpoint arrest caused by a double-strand break via a centromere-dependent mechanism. Curr. Biol. 20:328–32
     [Google Scholar]
  106. 106. 
    Grenon M, Costelloe T, Jimeno S, O'Shaughnessy A, Fitzgerald J et al. 2007. Docking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain. Yeast 24:105–19
     [Google Scholar]
  107. 107. 
    Hammet A, Magill C, Heierhorst J, Jackson SP 2007. Rad9 BRCT domain interaction with phosphorylated H2AX regulates the G1 checkpoint in budding yeast. EMBO Rep 8:851–57
     [Google Scholar]
  108. 108. 
    Giannattasio M, Lazzaro F, Plevani P, Muzi-Falconi M 2005. The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J. Biol. Chem. 280:9879–86
     [Google Scholar]
  109. 109. 
    van Leeuwen F, Gafken PR, Gottschling DE 2002. Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell 109:745–56
     [Google Scholar]
  110. 110. 
    Granata M, Lazzaro F, Novarina D, Panigada D, Puddu F et al. 2010. Dynamics of Rad9 chromatin binding and checkpoint function are mediated by its dimerization and are cell cycle–regulated by CDK1 activity. PLOS Genet 6:e1001047
     [Google Scholar]
  111. 111. 
    Pfander B, Diffley JF. 2011. Dpb11 coordinates Mec1 kinase activation with cell cycle-regulated Rad9 recruitment. EMBO J 30:4897–907
     [Google Scholar]
  112. 112. 
    Gritenaite D, Princz LN, Szakal B, Bantele SC, Wendeler L et al. 2014. A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replication. Genes Dev 28:1604–19
     [Google Scholar]
  113. 113. 
    Puddu F, Granata M, Di Nola L, Balestrini A, Piergiovanni G et al. 2008. Phosphorylation of the budding yeast 9–1–1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint. Mol. Cell. Biol. 28:4782–93
     [Google Scholar]
  114. 114. 
    di Cicco G, Bantele SCS, Reusswig KU, Pfander B 2017. A cell cycle-independent mode of the Rad9-Dpb11 interaction is induced by DNA damage. Sci. Rep. 7:11650
     [Google Scholar]
  115. 115. 
    Sun Z, Hsiao J, Fay DS, Stern DF 1998. Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Science 281:272–74
     [Google Scholar]
  116. 116. 
    Usui T, Foster SS, Petrini JH 2009. Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization. Mol. Cell 33:147–59
     [Google Scholar]
  117. 117. 
    Goldberg M, Stucki M, Falck J, D'Amours D, Rahman D et al. 2003. MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature 421:952–56
     [Google Scholar]
  118. 118. 
    Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ 2003. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 421:961–66
     [Google Scholar]
  119. 119. 
    Wu L, Luo K, Lou Z, Chen J 2008. MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks. PNAS 105:11200–5
     [Google Scholar]
  120. 120. 
    Peng A, Chen PL. 2003. NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage. J. Biol. Chem. 278:8873–76
     [Google Scholar]
  121. 121. 
    Wang B, Matsuoka S, Carpenter PB, Elledge SJ 2002. 53BP1, a mediator of the DNA damage checkpoint. Science 298:1435–38
     [Google Scholar]
  122. 122. 
    Her J, Ray C, Altshuler J, Zheng H, Bunting SF 2018. 53BP1 mediates ATR-Chk1 signaling and protects replication forks under conditions of replication stress. Mol. Cell. Biol. 38:e00472–17
     [Google Scholar]
  123. 123. 
    Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP 2005. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123:1213–26
     [Google Scholar]
  124. 124. 
    Baldock RA, Day M, Wilkinson OJ, Cloney R, Jeggo PA et al. 2015. ATM localization and heterochromatin repair depend on direct interaction of the 53BP1-BRCT2 domain with γH2AX. Cell Rep 13:2081–89
     [Google Scholar]
  125. 125. 
    Kleiner RE, Verma P, Molloy KR, Chait BT, Kapoor TM 2015. Chemical proteomics reveals a γH2AX-53BP1 interaction in the DNA damage response. Nat. Chem. Biol. 11:807–14
     [Google Scholar]
  126. 126. 
    Wang J, Gong Z, Chen J 2011. MDC1 collaborates with TopBP1 in DNA replication checkpoint control. J. Cell Biol. 193:267–73
     [Google Scholar]
  127. 127. 
    Leung CC, Sun L, Gong Z, Burkat M, Edwards R et al. 2013. Structural insights into recognition of MDC1 by TopBP1 in DNA replication checkpoint control. Structure 21:1450–59
     [Google Scholar]
  128. 128. 
    Cescutti R, Negrini S, Kohzaki M, Halazonetis TD 2010. TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint. EMBO J 29:3723–32
     [Google Scholar]
  129. 129. 
    Liu Y, Cussiol JR, Dibitetto D, Sims JR, Twayana S et al. 2017. TOPBP1Dpb11 plays a conserved role in homologous recombination DNA repair through the coordinated recruitment of 53BP1Rad9. J. Cell Biol. 216:623–39
     [Google Scholar]
  130. 130. 
    Ferrari M, Dibitetto D, De Gregorio G, Eapen VV, Rawal CC et al. 2015. Functional interplay between the 53BP1-ortholog Rad9 and the Mre11 complex regulates resection, end-tethering and repair of a double-strand break. PLOS Genet 11:e1004928
     [Google Scholar]
  131. 131. 
    Bunting SF, Callen E, Wong N, Chen HT, Polato F et al. 2010. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141:243–54
     [Google Scholar]
  132. 132. 
    Hustedt N, Durocher D. 2016. The control of DNA repair by the cell cycle. Nat. Cell Biol. 19:1–9
     [Google Scholar]
  133. 133. 
    Alcasabas AA, Osborn AJ, Bachant J, Hu F, Werler PJ et al. 2001. Mrc1 transduces signals of DNA replication stress to activate Rad53. Nat. Cell Biol. 3:958–65
     [Google Scholar]
  134. 134. 
    Kumagai A, Dunphy WG. 2000. Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts. Mol. Cell 6:839–49
     [Google Scholar]
  135. 135. 
    Zhao X, Chabes A, Domkin V, Thelander L, Rothstein R 2001. The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage. EMBO J 20:3544–53
     [Google Scholar]
  136. 136. 
    Desany BA, Alcasabas AA, Bachant JB, Elledge SJ 1998. Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Genes Dev 12:2956–70
     [Google Scholar]
  137. 137. 
    Zhao X, Muller EG, Rothstein R 1998. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol. Cell 2:329–40
     [Google Scholar]
  138. 138. 
    Huang M, Zhou Z, Elledge SJ 1998. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell 94:595–605
     [Google Scholar]
  139. 139. 
    Jaehnig EJ, Kuo D, Hombauer H, Ideker TG, Kolodner RD 2013. Checkpoint kinases regulate a global network of transcription factors in response to DNA damage. Cell Rep 4:174–88
     [Google Scholar]
  140. 140. 
    Travesa A, Kuo D, de Bruin RA, Kalashnikova TI, Guaderrama M et al. 2012. DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1. EMBO J 31:1811–22
     [Google Scholar]
  141. 141. 
    Bastos de Oliveira FM, Harris MR, Brazauskas P, de Bruin RA, Smolka MB 2012. Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes. EMBO J 31:1798–810
     [Google Scholar]
  142. 142. 
    Edenberg ER, Vashisht A, Benanti JA, Wohlschlegel J, Toczyski DP 2014. Rad53 downregulates mitotic gene transcription by inhibiting the transcriptional activator Ndd1. Mol. Cell. Biol. 34:725–38
     [Google Scholar]
  143. 143. 
    Kim EM, Jang YK, Park SD 2002. Phosphorylation of Rph1, a damage-responsive repressor of PHR1 in Saccharomyces cerevisiae, is dependent upon Rad53 kinase. Nucleic Acids Res 30:643–48
     [Google Scholar]
  144. 144. 
    Eapen VV, Waterman DP, Bernard A, Schiffmann N, Sayas E et al. 2017. A pathway of targeted autophagy is induced by DNA damage in budding yeast. PNAS 114:E1158–E67
     [Google Scholar]
  145. 145. 
    Allen JB, Zhou Z, Siede W, Friedberg EC, Elledge SJ 1994. The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev 8:2401–15
     [Google Scholar]
  146. 146. 
    Game JC. 1975. Radiation-sensitive mutants of yeast. Basic Life Sci 5B:541–44
     [Google Scholar]
  147. 147. 
    Schwartz MF, Lee SJ, Duong JK, Eminaga S, Stern DF 2003. FHA domain-mediated DNA checkpoint regulation of Rad53. Cell Cycle 2:384–96
     [Google Scholar]
  148. 148. 
    Sweeney FD, Yang F, Chi A, Shabanowitz J, Hunt DF, Durocher D 2005. Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Curr. Biol. 15:1364–75
     [Google Scholar]
  149. 149. 
    Schwartz MF, Duong JK, Sun Z, Morrow JS, Pradhan D, Stern DF 2002. Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Mol. Cell 9:1055–65
     [Google Scholar]
  150. 150. 
    Chen ESW, Hoch NC, Wang SC, Pellicioli A, Heierhorst J, Tsai MD 2014. Use of quantitative mass spectrometric analysis to elucidate the mechanisms of phospho-priming and auto-activation of the checkpoint kinase Rad53 in vivo. Mol Cell Proteom 13:551–65
     [Google Scholar]
  151. 151. 
    Ma NJL, Stern DF 2008. Regulation of the Rad53 protein kinase in signal amplification by oligomer assembly and disassembly. Cell Cycle 7:808–17
     [Google Scholar]
  152. 152. 
    Morrison AJ, Kim JA, Person MD, Highland J, Xiao J et al. 2007. Mec1/Tel1 phosphorylation of the INO80 chromatin remodeling complex influences DNA damage checkpoint responses. Cell 130:499–511
     [Google Scholar]
  153. 153. 
    Morrison AJ, Shen X. 2009. Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. Nat. Rev. Mol. Cell Biol. 10:373–84
     [Google Scholar]
  154. 154. 
    Kapoor P, Bao Y, Xiao J, Espejo A, Yang L et al. 2015. Phosphorylation-dependent enhancement of Rad53 kinase activity through the INO80 chromatin remodeling complex. Mol. Cell 58:863–69
     [Google Scholar]
  155. 155. 
    Sanchez Y, Bachant J, Wang H, Hu F, Liu D et al. 1999. Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science 286:1166–71
     [Google Scholar]
  156. 156. 
    Blankley RT, Lydall D. 2004. A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J. Cell Sci. 117:601–8
     [Google Scholar]
  157. 157. 
    Abreu CM, Kumar R, Hamilton D, Dawdy AW, Creavin K et al. 2013. Site-specific phosphorylation of the DNA damage response mediator rad9 by cyclin-dependent kinases regulates activation of checkpoint kinase 1. PLOS Genet 9:e1003310
     [Google Scholar]
  158. 158. 
    Toczyski DP, Galgoczy DJ, Hartwell LH 1997. CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 90:1097–106
     [Google Scholar]
  159. 159. 
    Dewar JM, Lydall D. 2012. Similarities and differences between “uncapped” telomeres and DNA double-strand breaks. Chromosoma 121:117–30
     [Google Scholar]
  160. 160. 
    Harper JW, Elledge SJ. 2007. The DNA damage response: ten years after. Mol. Cell 28:739–45
     [Google Scholar]
  161. 161. 
    Cuadrado M, Martinez-Pastor B, Murga M, Toledo LI, Gutierrez-Martinez P et al. 2006. ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J. Exp. Med. 203:297–303
     [Google Scholar]
  162. 162. 
    Shiotani B, Zou L. 2009. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol. Cell 33:547–58
     [Google Scholar]
  163. 163. 
    Bartek J, Lukas J. 2003. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3:421–49
     [Google Scholar]
  164. 164. 
    Schwarz JK, Lovly CM, Piwnica-Worms H 2003. Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation. Mol. Cancer Res. 1:598–609
     [Google Scholar]
  165. 165. 
    Xu X, Tsvetkov LM, Stern DF 2002. Chk2 activation and phosphorylation-dependent oligomerization. Mol. Cell. Biol. 22:4419–32
     [Google Scholar]
  166. 166. 
    Ng CP, Lee HC, Ho CW, Arooz T, Siu WY et al. 2004. Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains. J. Biol. Chem. 279:8808–19
     [Google Scholar]
  167. 167. 
    Ahn JY, Schwarz JK, Piwnica-Worms H, Canman CE 2000. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res 60:5934–36
     [Google Scholar]
  168. 168. 
    Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D et al. 2000. Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint. Genes Dev 14:1448–59
     [Google Scholar]
  169. 169. 
    Zhao H, Piwnica-Worms H. 2001. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol. Cell. Biol. 21:4129–39
     [Google Scholar]
  170. 170. 
    Buisson R, Boisvert JL, Benes CH, Zou L 2015. Distinct but concerted roles of ATR, DNA-PK, and Chk1 in countering replication stress during S phase. Mol. Cell 59:1011–24
     [Google Scholar]
  171. 171. 
    Giono LE, Manfredi JJ. 2006. The p53 tumor suppressor participates in multiple cell cycle checkpoints. J. Cell Physiol. 209:13–20
     [Google Scholar]
  172. 172. 
    Carvajal LA, Manfredi JJ. 2013. Another fork in the road—life or death decisions by the tumour suppressor p53. EMBO Rep 14:414–21
     [Google Scholar]
  173. 173. 
    Lukas J, Lukas C, Bartek J 2004. Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. DNA Repair 3:997–1007
     [Google Scholar]
  174. 174. 
    Boehme KA, Blattner C. 2009. Regulation of p53—insights into a complex process. Crit. Rev. Biochem. Mol. Biol. 44:367–92
     [Google Scholar]
  175. 175. 
    Boutros R, Dozier C, Ducommun B 2006. The when and wheres of CDC25 phosphatases. Curr. Opin. Cell Biol. 18:185–91
     [Google Scholar]
  176. 176. 
    Sorensen CS, Syljuasen RG. 2012. Safeguarding genome integrity: the checkpoint kinases ATR, CHK1 and WEE1 restrain CDK activity during normal DNA replication. Nucleic Acids Res 40:477–86
     [Google Scholar]
  177. 177. 
    Cohen-Fix O, Koshland D. 1997. The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway. PNAS 94:14361–66
     [Google Scholar]
  178. 178. 
    Yamamoto A, Guacci V, Koshland D 1996. Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s). J. Cell Biol. 133:99–110
     [Google Scholar]
  179. 179. 
    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]
  180. 180. 
    Shirayama M, Toth A, Galova M, Nasmyth K 1999. APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Nature 402:203–7
     [Google Scholar]
  181. 181. 
    Agarwal R, Tang Z, Yu H, Cohen-Fix O 2003. Two distinct pathways for inhibiting pds1 ubiquitination in response to DNA damage. J. Biol. Chem. 278:45027–33
     [Google Scholar]
  182. 182. 
    Gardner R, Putnam CW, Weinert T 1999. RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. EMBO J 18:3173–85
     [Google Scholar]
  183. 183. 
    Dotiwala F, Eapen VV, Harrison JC, Arbel-Eden A, Ranade V et al. 2013. DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase. PNAS 110:E41–49
     [Google Scholar]
  184. 184. 
    Bartek J, Falck J, Lukas J 2001. CHK2 kinase—a busy messenger. Nat. Rev. Mol. Cell Biol. 2:877–86
     [Google Scholar]
  185. 185. 
    Bastos de Oliveira FM, Kim D, Cussiol JR, Das J, Jeong MC et al. 2015. Phosphoproteomics reveals distinct modes of Mec1/ATR signaling during DNA replication. Mol. Cell 57:1124–32
     [Google Scholar]
  186. 186. 
    Gapud EJ, Sleckman BP. 2011. Unique and redundant functions of ATM and DNA-PKcs during V(D)J recombination. Cell Cycle 10:1928–35
     [Google Scholar]
  187. 187. 
    Zha S, Jiang W, Fujiwara Y, Patel H, Goff PH et al. 2011. Ataxia telangiectasia-mutated protein and DNA-dependent protein kinase have complementary V(D)J recombination functions. PNAS 108:2028–33
     [Google Scholar]
  188. 188. 
    Gapud EJ, Dorsett Y, Yin B, Callen E, Bredemeyer A et al. 2011. Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation. PNAS 108:2022–27
     [Google Scholar]
  189. 189. 
    Jette N, Lees-Miller SP. 2015. The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis. Prog. Biophys. Mol. Biol. 117:194–205
     [Google Scholar]
  190. 190. 
    Setiaputra D, Durocher D. 2019. Shieldin—the protector of DNA ends. EMBO Rep20e47560
     [Google Scholar]
  191. 191. 
    Jachimowicz RD, Beleggia F, Isensee J, Velpula BB, Goergens J et al. 2019. UBQLN4 represses homologous recombination and is overexpressed in aggressive tumors. Cell 176:505–19.e22
     [Google Scholar]
  192. 192. 
    Shibata A, Conrad S, Birraux J, Geuting V, Barton O et al. 2011. Factors determining DNA double-strand break repair pathway choice in G2 phase. EMBO J 30:1079–92
     [Google Scholar]
  193. 193. 
    Vriend LE, Prakash R, Chen CC, Vanoli F, Cavallo F et al. 2016. Distinct genetic control of homologous recombination repair of Cas9-induced double-strand breaks, nicks and paired nicks. Nucleic Acids Res 44:5204–17
     [Google Scholar]
  194. 194. 
    Kass EM, Helgadottir HR, Chen CC, Barbera M, Wang R et al. 2013. Double-strand break repair by homologous recombination in primary mouse somatic cells requires BRCA1 but not the ATM kinase. PNAS 110:5564–69
     [Google Scholar]
  195. 195. 
    Pierce AJ, Johnson RD, Thompson LH, Jasin M 1999. XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes Dev 13:2633–38
     [Google Scholar]
  196. 196. 
    Buisson R, Niraj J, Rodrigue A, Ho CK, Kreuzer J et al. 2017. Coupling of homologous recombination and the checkpoint by ATR. Mol. Cell 65:336–46
     [Google Scholar]
  197. 197. 
    Kim D, Liu Y, Oberly S, Freire R, Smolka MB 2018. ATR-mediated proteome remodeling is a major determinant of homologous recombination capacity in cancer cells. Nucleic Acids Res 46:8311–25
     [Google Scholar]
  198. 198. 
    Lanz MC, Dibitetto D, Smolka MB 2019. DNA damage kinase signaling: checkpoint and repair at 30 years. EMBO J 38:e101801
     [Google Scholar]
  199. 199. 
    Szakal B, Branzei D. 2013. Premature Cdk1/Cdc5/Mus81 pathway activation induces aberrant replication and deleterious crossover. EMBO J 32:1155–67
     [Google Scholar]
  200. 200. 
    Pellicioli A, Lee SE, Lucca C, Foiani M, Haber JE 2001. Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage–induced G2/M arrest. Mol. Cell 7:293–300
     [Google Scholar]
  201. 201. 
    Palou R, Palou G, Quintana DG 2017. A role for the spindle assembly checkpoint in the DNA damage response. Curr. Genet. 63:275–80
     [Google Scholar]
  202. 202. 
    Kim JA, Hicks WM, Li J, Tay SY, Haber JE 2011. Protein phosphatases pph3, ptc2, and ptc3 play redundant roles in DNA double-strand break repair by homologous recombination. Mol. Cell. Biol. 31:507–16
     [Google Scholar]
  203. 203. 
    Gobbini E, Villa M, Gnugnoli M, Menin L, Clerici M, Longhese MP 2015. Sae2 function at DNA double-strand breaks is bypassed by dampening Tel1 or Rad53 activity. PLOS Genet 11:e1005685
     [Google Scholar]
  204. 204. 
    Ohouo PY, Bastos de Oliveira FM, Liu Y, Ma CJ, Smolka MB 2013. DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9. Nature 493:120–24
     [Google Scholar]
  205. 205. 
    Ramos F, Villoria MT, Alonso-Rodriguez E, Clemente-Blanco A 2019. Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response. Cell Stress 3:70–85
     [Google Scholar]
  206. 206. 
    Dibitetto D, Ferrari M, Rawal CC, Balint A, Kim T et al. 2016. Slx4 and Rtt107 control checkpoint signalling and DNA resection at double-strand breaks. Nucleic Acids Res 44:669–82
     [Google Scholar]
  207. 207. 
    Millan-Zambrano G, Santos-Rosa H, Puddu F, Robson SC, Jackson SP, Kouzarides T 2018. Phosphorylation of histone H4T80 triggers DNA damage checkpoint recovery. Mol. Cell 72:625–35.e4
     [Google Scholar]
  208. 208. 
    Lee SE, Moore JK, Holmes A, Umezu K, Kolodner RD, Haber JE 1998. Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Cell 94:399–409
     [Google Scholar]
  209. 209. 
    Blank HM, Sheltzer JM, Meehl CM, Amon A 2015. Mitotic entry in the presence of DNA damage is a widespread property of aneuploidy in yeast. Mol. Biol. Cell 26:1440–51
     [Google Scholar]
  210. 210. 
    Syljuasen RG, Jensen S, Bartek J, Lukas J 2006. Adaptation to the ionizing radiation–induced G2 checkpoint occurs in human cells and depends on checkpoint kinase 1 and Polo-like kinase 1 kinases. Cancer Res 66:10253–57
     [Google Scholar]
  211. 211. 
    Memisoglu G, Lanz MC, Eapen VV, Jordan JM, Lee K et al. 2019. Mec1(ATR) autophosphorylation and Ddc2(ATRIP) phosphorylation regulates DNA damage checkpoint signaling. Cell Rep 28:1090–102.e3
     [Google Scholar]
  212. 212. 
    Leroy C, Lee SE, Vaze MB, Ochsenbein F, Guerois R et al. 2003. PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break. Mol. Cell 11:827–35
     [Google Scholar]
  213. 213. 
    Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D et al. 2006. A phosphatase complex that dephosphorylates γH2AX regulates DNA damage checkpoint recovery. Nature 439:497–501
     [Google Scholar]
  214. 214. 
    Lee SE, Pellicioli A, Vaze MB, Sugawara N, Malkova A et al. 2003. Yeast Rad52 and Rad51 recombination proteins define a second pathway of DNA damage assessment in response to a single double-strand break. Mol. Cell. Biol. 23:8913–23
     [Google Scholar]
  215. 215. 
    Rawal CC, Riccardo S, Pesenti C, Ferrari M, Marini F, Pellicioli A 2016. Reduced kinase activity of polo kinase Cdc5 affects chromosome stability and DNA damage response in S. cerevisiae. Cell Cycle 15:2906–19
     [Google Scholar]
  216. 216. 
    Jazayeri A, Balestrini A, Garner E, Haber JE, Costanzo V 2008. Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity. EMBO J 27:1953–62
     [Google Scholar]
  217. 217. 
    Clerici M, Mantiero D, Lucchini G, Longhese MP 2006. The Saccharomyces cerevisiae Sae2 protein negatively regulates DNA damage checkpoint signalling. EMBO Rep 7:212–18
     [Google Scholar]
  218. 218. 
    Eapen VV, Sugawara N, Tsabar M, Wu WH, Haber JE 2012. The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end resection and checkpoint deactivation. Mol. Cell. Biol. 32:4727–40
     [Google Scholar]
  219. 219. 
    Kotsantis P, Petermann E, Boulton SJ 2018. Mechanisms of oncogene-induced replication stress: jigsaw falling into place. Cancer Discov 8:537–55
     [Google Scholar]
  220. 220. 
    Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:646–74
     [Google Scholar]
  221. 221. 
    Negrini S, Gorgoulis VG, Halazonetis TD 2010. Genomic instability—an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 11:220–28
     [Google Scholar]
  222. 222. 
    Choi M, Kipps T, Kurzrock R 2016. ATM mutations in cancer: therapeutic implications. Mol. Cancer Ther. 15:1781–91
     [Google Scholar]
  223. 223. 
    Olivier M, Hollstein M, Hainaut P 2010. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb. Perspect. Biol. 2:a001008
     [Google Scholar]
  224. 224. 
    Bailey MH, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D et al. 2018. Comprehensive characterization of cancer driver genes and mutations. Cell 173:371–85.e18
     [Google Scholar]
  225. 225. 
    Lecona E, Fernandez-Capetillo O. 2018. Targeting ATR in cancer. Nat. Rev. Cancer 18:586–95
     [Google Scholar]
  226. 226. 
    Fishler T, Li YY, Wang RH, Kim HS, Sengupta K et al. 2010. Genetic instability and mammary tumor formation in mice carrying mammary-specific disruption of Chk1 and p53. Oncogene 29:4007–17
     [Google Scholar]
  227. 227. 
    Tho LM, Libertini S, Rampling R, Sansom O, Gillespie DA 2012. Chk1 is essential for chemical carcinogen-induced mouse skin tumorigenesis. Oncogene 31:1366–75
     [Google Scholar]
  228. 228. 
    Hickson I, Zhao Y, Richardson CJ, Green SJ, Martin NM et al. 2004. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 64:9152–59
     [Google Scholar]
  229. 229. 
    Charrier JD, Durrant SJ, Golec JM, Kay DP, Knegtel RM et al. 2011. Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J. Med. Chem. 54:2320–30
     [Google Scholar]
  230. 230. 
    Weber AM, Ryan AJ. 2015. ATM and ATR as therapeutic targets in cancer. Pharmacol. Ther. 149:124–38
     [Google Scholar]
  231. 231. 
    Pilie PG, Tang C, Mills GB, Yap TA 2019. State-of-the-art strategies for targeting the DNA damage response in cancer. Nat. Rev. Clin. Oncol. 16:81–104
     [Google Scholar]
  232. 232. 
    Ihry RJ, Worringer KA, Salick MR, Frias E, Ho D et al. 2018. p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells. Nat. Med. 24:939–46
     [Google Scholar]
  233. 233. 
    Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J 2018. CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response. Nat. Med. 24:927–30
     [Google Scholar]
  234. 234. 
    Niu D, Wei HJ, Lin L, George H, Wang T et al. 2017. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science 357:1303–7
     [Google Scholar]
  235. 235. 
    Brown KR, Mair B, Soste M, Moffat J 2019. CRISPR screens are feasible in TP53 wild-type cells. Mol. Syst. Biol. 15:e8679
     [Google Scholar]
  236. 236. 
    Schiroli G, Conti A, Ferrari S, Della Volpe L, Jacob A et al. 2019. Precise gene editing preserves hematopoietic stem cell function following transient p53-mediated DNA damage response. Cell Stem Cell 24:551–65.e8
     [Google Scholar]
  237. 237. 
    Ho B, Baryshnikova A, Brown GW 2018. Unification of protein abundance datasets yields a quantitative Saccharomyces cerevisiae proteome. Cell Syst 6:192–205.e3
     [Google Scholar]
  238. 238. 
    Hustedt N, Seeber A, Sack R, Tsai-Pflugfelder M, Bhullar B et al. 2015. Yeast PP4 interacts with ATR homolog Ddc2-Mec1 and regulates checkpoint signaling. Mol. Cell 57:273–89
     [Google Scholar]
  239. 239. 
    Yu TY, Kimble MT, Symington LS 2018. Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection. PNAS 115:E11961–E69
     [Google Scholar]
  240. 240. 
    Colombo CV, Menin L, Ranieri R, Bonetti D, Clerici M, Longhese MP 2019. Uncoupling Sae2 functions in downregulation of Tel1 and Rad53 signaling activities. Genetics 211:515–30
     [Google Scholar]
/content/journals/10.1146/annurev-biochem-011520-104722
Loading
Checkpoint Responses to DNA Double-Strand Breaks
Annual Review of Biochemistry 89, 103 (2020); https://doi.org/10.1146/annurev-biochem-011520-104722
/content/journals/10.1146/annurev-biochem-011520-104722
/content/journals/10.1146/annurev-biochem-011520-104722
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error