1932

Abstract

The repair of DNA by homologous recombination is an essential, efficient, and high-fidelity process that mends DNA lesions formed during cellular metabolism; these lesions include double-stranded DNA breaks, daughter-strand gaps, and DNA cross-links. Genetic defects in the homologous recombination pathway undermine genomic integrity and cause the accumulation of gross chromosomal abnormalities—including rearrangements, deletions, and aneuploidy—that contribute to cancer formation. Recombination proceeds through the formation of joint DNA molecules—homologously paired but metastable DNA intermediates that are processed by several alternative subpathways—making recombination a versatile and robust mechanism to repair damaged chromosomes. Modern biophysical methods make it possible to visualize, probe, and manipulate the individual molecules participating in the intermediate steps of recombination, revealing new details about the mechanics of genetic recombination. We review and discuss the individual stages of homologous recombination, focusing on common pathways in bacteria, yeast, and humans, and place particular emphasis on the molecular mechanisms illuminated by single-molecule methods.

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 4

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 5

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 2

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 9

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 7

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 8

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 1

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 6

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 3

Associated Article

There are media items related to this article:
Mechanics and Single-Molecule Interrogation of DNA Recombination: Supplemental Video 10
Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-060614-034352
2016-06-02
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/biochem/85/1/annurev-biochem-060614-034352.html?itemId=/content/journals/10.1146/annurev-biochem-060614-034352&mimeType=html&fmt=ahah

Literature Cited

  1. Ciccia A, Elledge SJ. 1.  2010. The DNA damage response: making it safe to play with knives. Mol. Cell 40:179–204 [Google Scholar]
  2. Drake JW, Charlesworth B, Charlesworth D, Crow JF. 2.  1998. Rates of spontaneous mutation. Genetics 148:1667–86 [Google Scholar]
  3. Hoeijmakers JH. 3.  2009. DNA damage, aging, and cancer. N. Engl. J. Med. 361:1475–85 [Google Scholar]
  4. Sanz MM, German J. 4.  1993. GeneReviews RA Pagon, MP Adam, HH Ardinger, SE Wallace, A Amemiya, et al. Seattle (WA)
  5. Kottemann MC, Smogorzewska A. 5.  2013. Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature 493:356–63 [Google Scholar]
  6. Bizard AH, Hickson ID. 6.  2014. The dissolution of double Holliday junctions. Cold Spring Harb. Perspect. Biol. 6:a016477 [Google Scholar]
  7. Kogoma T. 7.  1997. Stable DNA replication: interplay between DNA replication, homologous recombination, and transcription. Microbiol. Mol. Biol. Rev. 61:212–38 [Google Scholar]
  8. Kowalczykowski SC. 8.  2000. Initiation of genetic recombination and recombination-dependent replication. Trends Biochem. Sci. 25:156–65 [Google Scholar]
  9. Kuzminov A. 9.  1996. Recombinational Repair of DNA Damage Austin, TX: RG Landes
  10. Cox MM, Goodman MF, Kreuzer KN, Sherratt DJ, Sandler SJ, Marians KJ. 10.  2000. The importance of repairing stalled replication forks. Nature 404:37–41 [Google Scholar]
  11. Vilenchik MM, Knudson AG. 11.  2003. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. PNAS 100:12871–76 [Google Scholar]
  12. Bzymek M, Thayer NH, Oh SD, Kleckner N, Hunter N. 12.  2010. Double Holliday junctions are intermediates of DNA break repair. Nature 464:937–41 [Google Scholar]
  13. Wolff S. 13.  1977. Sister chromatid exchange. Annu. Rev. Genet. 11:183–201 [Google Scholar]
  14. Chaganti RS, Schonberg S, German J. 14.  1974. A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes. PNAS 71:4508–12 [Google Scholar]
  15. Wyatt HD, West SC. 15.  2014. Holliday junction resolvases. Cold Spring Harb. Perspect. Biol. 6a023192
  16. Clark AJ, Margulies AD. 16.  1965. Isolation and characterization of recombination-deficient mutants of Escherichia coli K12. PNAS 53:451–59 [Google Scholar]
  17. Kowalczykowski SC. 17.  2015. An overview of the molecular mechanisms of recombinational DNA repair. Cold Spring Harb Perspect. Biol. 7:a016410 [Google Scholar]
  18. Heyer WD. 18.  2015. Regulation of recombination and genomic maintenance. Cold Spring Harb. Perspect. Biol. 7a016501
  19. Amitani I, Liu B, Dombrowski CC, Baskin RJ, Kowalczykowski SC. 19.  2010. Watching individual proteins acting on single molecules of DNA. Methods Enzymol. 472:261–91 [Google Scholar]
  20. Forget AL, Dombrowski CC, Amitani I, Kowalczykowski SC. 20.  2013. Exploring protein–DNA interactions in 3D using in situ construction, manipulation and visualization of individual DNA dumbbells with optical traps, microfluidics and fluorescence microscopy. Nat. Protoc. 8:525–38 [Google Scholar]
  21. Bustamante C, Bryant Z, Smith SB. 21.  2003. Ten years of tension: single-molecule DNA mechanics. Nature 421:423–27 [Google Scholar]
  22. Ha T, Kozlov AG, Lohman TM. 22.  2012. Single-molecule views of protein movement on single-stranded DNA. Annu. Rev. Biophys. 41:295–319 [Google Scholar]
  23. van Oijen AM, Loparo JJ. 23.  2010. Single-molecule studies of the replisome. Annu. Rev. Biophys. 39:429–48 [Google Scholar]
  24. Bustamante C, Cheng W, Mejia YX. 24.  2011. Revisiting the central dogma one molecule at a time. Cell 144:480–97 [Google Scholar]
  25. Duzdevich D, Redding S, Greene EC. 25.  2014. DNA dynamics and single-molecule biology. Chem. Rev. 114:3072–86 [Google Scholar]
  26. Perkins TT, Quake SR, Smith DE, Chu S. 26.  1994. Relaxation of a single DNA molecule observed by optical microscopy. Science 264:822–26 [Google Scholar]
  27. Brewer LR, Bianco PR. 27.  2008. Laminar flow cells for single-molecule studies of DNA–protein interactions. Nat. Methods 5:517–25 [Google Scholar]
  28. Bianco PR, Brewer LR, Corzett M, Balhorn R, Yeh Y. 28.  et al. 2001. Processive translocation and DNA unwinding by individual RecBCD enzyme molecules. Nature 409:374–78 [Google Scholar]
  29. Galletto R, Amitani I, Baskin RJ, Kowalczykowski SC. 29.  2006. Direct observation of individual RecA filaments assembling on single DNA molecules. Nature 443:875–78 [Google Scholar]
  30. Liu B, Baskin RJ, Kowalczykowski SC. 30.  2013. DNA unwinding heterogeneity by RecBCD results from static molecules able to equilibrate. Nature 500:482–85 [Google Scholar]
  31. Fordyce PM, Valentine MT, Block SM. 31.  2008. Advances in surface-based assays for single molecules. Single-Molecule Techniques: A Laboratory Manual P Selvin, T Ha 20431–460 Cold Spring Harbor, NY: Cold Spring Harb. Lab. [Google Scholar]
  32. Ha T, Enderle T, Ogletree DF, Chemla DS, Selvin PR, Weiss S. 32.  1996. Probing the interaction between two single molecules: fluorescence resonance energy transfer between a single donor and a single acceptor. PNAS 93:6264–68 [Google Scholar]
  33. Joo C, Balci H, Ishitsuka Y, Buranachai C, Ha T. 33.  2008. Advances in single-molecule fluorescence methods for molecular biology. Annu. Rev. Biochem. 77:51–76 [Google Scholar]
  34. Léger JF, Romano G, Sarkar A, Robert J, Bourdieu L. 34.  et al. 1999. Structural transitions of a twisted and stretched DNA molecule. Phys. Rev. Lett. 83:1066–69 [Google Scholar]
  35. Neuman KC, Block SM. 35.  2004. Optical trapping. Rev. Sci. Instrum. 75:2787–809 [Google Scholar]
  36. Zhou R, Kozlov AG, Roy R, Zhang J, Korolev S. 36.  et al. 2011. SSB functions as a sliding platform that migrates on DNA via reptation. Cell 146:222–32 [Google Scholar]
  37. Bryant Z, Oberstrass FC, Basu A. 37.  2012. Recent developments in single-molecule DNA mechanics. Curr. Opin. Struct. Biol. 22:304–12 [Google Scholar]
  38. Dillingham MS, Kowalczykowski SC. 38.  2008. RecBCD enzyme and the repair of double-stranded DNA breaks. Microbiol. Mol. Biol. Rev. 72:642–71 [Google Scholar]
  39. Singleton MR, Dillingham MS, Gaudier M, Kowalczykowski SC, Wigley DB. 39.  2004. Crystal structure of RecBCD enzyme reveals a machine for processing DNA breaks. Nature 432:187–93 [Google Scholar]
  40. Dillingham MS, Spies M, Kowalczykowski SC. 40.  2003. RecBCD enzyme is a bipolar DNA helicase. Nature 423:893–97 [Google Scholar]
  41. Taylor AF, Smith GR. 41.  2003. RecBCD enzyme is a DNA helicase with fast and slow motors of opposite polarity. Nature 423:889–93 [Google Scholar]
  42. Smith GR, Kunes SM, Schultz DW, Taylor A, Triman KL. 42.  1981. Structure of chi hotspots of generalized recombination. Cell 24:429–36 [Google Scholar]
  43. Arnold DA, Handa N, Kobayashi I, Kowalczykowski SC. 43.  2000. A novel, 11 nucleotide variant of χ, χ*: one of a class of sequences defining the Escherichia coli recombination hotspot χ. J. Mol. Biol. 300:469–79 [Google Scholar]
  44. Handa N, Yang L, Dillingham MS, Kobayashi I, Wigley DB, Kowalczykowski SC. 44.  2012. Molecular determinants responsible for recognition of the single-stranded DNA regulatory sequence, χ, by RecBCD enzyme. PNAS 109:8901–6 [Google Scholar]
  45. Yang L, Handa N, Liu B, Dillingham MS, Wigley DB, Kowalczykowski SC. 45.  2012. Alteration of χ recognition by RecBCD reveals a regulated molecular latch and suggests a channel-bypass mechanism for biological control. PNAS 109:8907–12 [Google Scholar]
  46. Stahl FW. 46.  2005. Chi: A little sequence controls a big enzyme. Genetics 170:487–93 [Google Scholar]
  47. Spies M, Bianco PR, Dillingham MS, Handa N, Baskin RJ, Kowalczykowski SC. 47.  2003. A molecular throttle: The recombination hotspot χ controls DNA translocation by the RecBCD helicase. Cell 114:647–54 [Google Scholar]
  48. Dixon DA, Kowalczykowski SC. 48.  1991. Homologous pairing in vitro stimulated by the recombination hotspot, Chi. Cell 66:361–71 [Google Scholar]
  49. Dixon DA, Kowalczykowski SC. 49.  1993. The recombination hotspot χ is a regulatory sequence that acts by attenuating the nuclease activity of the E. coli RecBCD enzyme. Cell 73:87–96 [Google Scholar]
  50. Dillingham MS, Webb MR, Kowalczykowski SC. 50.  2005. Bipolar DNA translocation contributes to highly processive DNA unwinding by RecBCD enzyme. J. Biol. Chem. 280:37069–77 [Google Scholar]
  51. Spies M, Dillingham MS, Kowalczykowski SC. 51.  2005. Translocation by the RecB motor is an absolute requirement for χ−recognition and RecA protein loading by RecBCD enzyme. J. Biol. Chem. 280:37078–87 [Google Scholar]
  52. Handa N, Bianco PR, Baskin RJ, Kowalczykowski SC. 52.  2005. Direct visualization of RecBCD movement reveals cotranslocation of the RecD motor after χ recognition. Mol. Cell 17:745–50 [Google Scholar]
  53. Spies M, Amitani I, Baskin RJ, Kowalczykowski SC. 53.  2007. RecBCD enzyme switches lead motor subunits in response to χ recognition. Cell 131:694–705 [Google Scholar]
  54. Wang J, Chen R, Julin DA. 54.  2000. A single nuclease active site of the Escherichia coli RecBCD enzyme catalyzes single-stranded DNA degradation in both directions. J. Biol. Chem. 275:507–13 [Google Scholar]
  55. Anderson DG, Kowalczykowski SC. 55.  1997. The translocating RecBCD enzyme stimulates recombination by directing RecA protein onto ssDNA in a χ-regulated manner. Cell 90:77–86 [Google Scholar]
  56. Arnold DA, Kowalczykowski SC. 56.  2000. Facilitated loading of RecA protein is essential to recombination by RecBCD enzyme. J. Biol. Chem. 275:12261–65 [Google Scholar]
  57. Spies M, Kowalczykowski SC. 57.  2006. The RecA binding locus of RecBCD is a general domain for recruitment of DNA strand exchange proteins. Mol. Cell 21:573–80 [Google Scholar]
  58. Levy A, Goren MG, Yosef I, Auster O, Manor M. 58.  et al. 2015. CRISPR adaptation biases explain preference for acquisition of foreign DNA. Nature 520:505–10 [Google Scholar]
  59. Finkelstein IJ, Visnapuu ML, Greene EC. 59.  2010. Single-molecule imaging reveals mechanisms of protein disruption by a DNA translocase. Nature 468:983–87 [Google Scholar]
  60. Eggleston AK, O'Neill TE, Bradbury EM, Kowalczykowski SC. 60.  1995. Unwinding of nucleosomal DNA by a DNA helicase. J. Biol. Chem. 270:2024–31 [Google Scholar]
  61. Chow KH, Courcelle J. 61.  2007. RecBCD and RecJ/RecQ initiate DNA degradation on distinct substrates in UV-irradiated Escherichia coli. Radiat. Res. 168:499–506 [Google Scholar]
  62. Pennington JM, Rosenberg SM. 62.  2007. Spontaneous DNA breakage in single living Escherichia coli cells. Nat. Genet. 39:797–802 [Google Scholar]
  63. Morimatsu K, Kowalczykowski SC. 63.  2014. RecQ helicase and RecJ nuclease provide complementary functions to resect DNA for homologous recombination. PNAS 111:E5133–42 [Google Scholar]
  64. Harmon FG, Kowalczykowski SC. 64.  2001. Biochemical characterization of the DNA helicase activity of the Escherichia coli RecQ helicase. J. Biol. Chem. 276:232–43 [Google Scholar]
  65. Shereda RD, Reiter NJ, Butcher SE, Keck JL. 65.  2009. Identification of the SSB binding site on E. coli RecQ reveals a conserved surface for binding SSB's C terminus. J. Mol. Biol. 386:612–25 [Google Scholar]
  66. Rad B, Kowalczykowski SC. 66.  2012. Translocation of E. coli RecQ helicase on single-stranded DNA. Biochemistry 51:2921–29 [Google Scholar]
  67. Rad B, Kowalczykowski SC. 67.  2012. Efficient coupling of ATP hydrolysis to translocation by RecQ helicase. PNAS 109:1443–48 [Google Scholar]
  68. Rad B, Forget AL, Baskin RJ, Kowalczykowski SC. 68.  2015. Single-molecule visualization of RecQ helicase reveals DNA melting, nucleation, and assembly are required for processive DNA unwinding. PNAS 112:50E6851–61 [Google Scholar]
  69. Byrd AK, Raney KD. 69.  2015. Fine tuning of a DNA fork by the RecQ helicase. PNAS 112:15263–64 [Google Scholar]
  70. Symington LS. 70.  2014. End resection at double-strand breaks: mechanism and regulation. Cold Spring Harb. Perspect. Biol. 6:a016436 [Google Scholar]
  71. Cannavo E, Cejka P. 71.  2014. Sae2 promotes dsDNA endonuclease activity within Mre11–Rad50–Xrs2 to resect DNA breaks. Nature 514:122–25 [Google Scholar]
  72. Cejka P, Kowalczykowski SC. 72.  2010. The full-length Saccharomyces cerevisiae Sgs1 protein is a vigorous DNA helicase that preferentially unwinds Holliday junctions. J. Biol. Chem. 285:8290–301 [Google Scholar]
  73. Masuda-Sasa T, Imamura O, Campbell JL. 73.  2006. Biochemical analysis of human Dna2. Nucleic Acids Res. 34:1865–75 [Google Scholar]
  74. Cejka P, Cannavo E, Polaczek P, Masuda-Sasa T, Pokharel S. 74.  et al. 2010. DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2. Nature 467:112–16 [Google Scholar]
  75. Niu H, Chung WH, Zhu Z, Kwon Y, Zhao W. 75.  et al. 2010. Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature 467:108–11 [Google Scholar]
  76. Levikova M, Klaue D, Seidel R, Cejka P. 76.  2013. Nuclease activity of Saccharomyces cerevisiae Dna2 inhibits its potent DNA helicase activity. PNAS 110:E1992–2001 [Google Scholar]
  77. Cannavo E, Cejka P, Kowalczykowski SC. 77.  2013. Relationship of DNA degradation by Saccharomyces cerevisiae exonuclease 1 and its stimulation by RPA and Mre11–Rad50–Xrs2 to DNA end resection. PNAS 110:E1661–68 [Google Scholar]
  78. Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL. 78.  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]
  79. Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC. 79.  2008. Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. PNAS 105:16906–11 [Google Scholar]
  80. Shim EY, Chung WH, Nicolette ML, Zhang Y, Davis M. 80.  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]
  81. Shereda RD, Kozlov AG, Lohman TM, Cox MM, Keck JL. 81.  2008. SSB as an organizer/mobilizer of genome maintenance complexes. Crit. Rev. Biochem. Mol. Biol. 43:289–318 [Google Scholar]
  82. Raghunathan S, Kozlov AG, Lohman TM, Waksman G. 82.  2000. Structure of the DNA binding domain of E. coli SSB bound to ssDNA. Nat. Struct. Biol. 7:648–52 [Google Scholar]
  83. Kowalczykowski SC, Krupp RA. 83.  1987. Effects of Escherichia coli SSB protein on the single-stranded DNA-dependent ATPase activity of Escherichia coli RecA protein: evidence that SSB protein facilitates the binding of RecA protein to regions of secondary structure within single-stranded DNA. J. Mol. Biol. 193:97–113 [Google Scholar]
  84. Roy R, Kozlov AG, Lohman TM, Ha T. 84.  2009. SSB protein diffusion on single-stranded DNA stimulates RecA filament formation. Nature 461:1092–97 [Google Scholar]
  85. Roy R, Kozlov AG, Lohman TM, Ha T. 85.  2007. Dynamic structural rearrangements between DNA binding modes of E. coli SSB protein. J. Mol. Biol. 369:1244–57 [Google Scholar]
  86. Lee KS, Marciel AB, Kozlov AG, Schroeder CM, Lohman TM, Ha T. 86.  2014. Ultrafast redistribution of E. coli SSB along long single-stranded DNA via intersegment transfer. J. Mol. Biol. 426:2413–21 [Google Scholar]
  87. Kozlov AG, Lohman TM. 87.  2002. Kinetic mechanism of direct transfer of Escherichia coli SSB tetramers between single-stranded DNA molecules. Biochemistry 41:11611–27 [Google Scholar]
  88. Bell JC, Liu B, Kowalczykowski SC. 88.  2015. Imaging and energetics of single SSB-ssDNA molecules reveal intramolecular condensation and insight into RecOR function. eLife 4:e08646 [Google Scholar]
  89. Chen R, Wold MS. 89.  2014. Replication protein A: single-stranded DNA's first responder: Dynamic DNA-interactions allow replication protein A to direct single-strand DNA intermediates into different pathways for synthesis or repair. BioEssays 36:1156–61 [Google Scholar]
  90. Wold MS. 90.  1997. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism. Annu. Rev. Biochem. 66:61–92 [Google Scholar]
  91. Bochkarev A, Bochkareva E, Frappier L, Edwards AM. 91.  1999. The crystal structure of the complex of replication protein A subunits RPA32 and RPA14 reveals a mechanism for single-stranded DNA binding. EMBO J. 18:4498–504 [Google Scholar]
  92. Bochkarev A, Pfuetzner RA, Edwards AM, Frappier L. 92.  1997. Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA. Nature 385:176–81 [Google Scholar]
  93. Nguyen B, Sokoloski J, Galletto R, Elson EL, Wold MS, Lohman TM. 93.  2014. Diffusion of human replication protein A along single-stranded DNA. J. Mol. Biol. 426:3246–61 [Google Scholar]
  94. Gibb B, Ye LF, Gergoudis SC, Kwon Y, Niu H. 94.  et al. 2014. Concentration-dependent exchange of replication protein A on single-stranded DNA revealed by single-molecule imaging. PLOS ONE 9:e87922 [Google Scholar]
  95. Kunzelmann S, Morris C, Chavda AP, Eccleston JF, Webb MR. 95.  2010. Mechanism of interaction between single-stranded DNA binding protein and DNA. Biochemistry 49:843–52 [Google Scholar]
  96. Bell JC, Plank JL, Dombrowski CC, Kowalczykowski SC. 96.  2012. Direct imaging of RecA nucleation and growth on single molecules of SSB-coated ssDNA. Nature 491:274–78 [Google Scholar]
  97. Sing CE, Olvera de la Cruz M, Marko JF. 97.  2014. Multiple-binding-site mechanism explains concentration-dependent unbinding rates of DNA-binding proteins. Nucleic Acids Res. 42:3783–91 [Google Scholar]
  98. Bell JC, Kowalczykowski SC. 98.  2015. RecA: regulation and mechanism of a molecular search engine. Trends Biochem. Sci. In press
  99. Umezu K, Chi NW, Kolodner RD. 99.  1993. Biochemical interaction of the Escherichia coli RecF, RecO, and RecR proteins with RecA protein and single-stranded DNA binding protein. PNAS 90:3875–79 [Google Scholar]
  100. Kowalczykowski SC, Clow J, Somani R, Varghese A. 100.  1987. Effects of the Escherichia coli SSB protein on the binding of Escherichia coli RecA protein to single-stranded DNA: demonstration of competitive binding and the lack of a specific protein–protein interaction. J. Mol. Biol. 193:81–95 [Google Scholar]
  101. Wegner A, Engel J. 101.  1975. Kinetics of the cooperative association of actin to actin filaments. Biophys. Chem. 3:215–25 [Google Scholar]
  102. Bryan J. 102.  1976. A quantitative analysis of microtubule elongation. J. Cell Biol. 71:749–67 [Google Scholar]
  103. Joo C, McKinney SA, Nakamura M, Rasnik I, Myong S, Ha T. 103.  2006. Real-time observation of RecA filament dynamics with single monomer resolution. Cell 126:515–27 [Google Scholar]
  104. Morimatsu K, Kowalczykowski SC. 104.  2003. RecFOR proteins load RecA protein onto gapped DNA to accelerate DNA strand exchange: a universal step of recombinational repair. Mol. Cell 11:1337–47 [Google Scholar]
  105. Blanar MA, Sandler SJ, Armengod ME, Ream LW, Clark AJ. 105.  1984. Molecular analysis of the recF gene of Escherichia coli. PNAS 81:4622–26 [Google Scholar]
  106. Morimatsu K, Wu Y, Kowalczykowski SC. 106.  2012. RecFOR proteins target RecA protein to a DNA gap with either DNA or RNA at the 5′ terminus: implication for repair of stalled replication forks. J. Biol. Chem. 287:35621–30 [Google Scholar]
  107. Sung P. 107.  1997. Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J. Biol. Chem. 272:28194–97 [Google Scholar]
  108. Shinohara A, Ogawa T. 108.  1998. Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature 391:404–7 [Google Scholar]
  109. New JH, Sugiyama T, Zaitseva E, Kowalczykowski SC. 109.  1998. Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A. Nature 391:407–10 [Google Scholar]
  110. Sugiyama T, New JH, Kowalczykowski SC. 110.  1998. DNA annealing by RAD52 protein is stimulated by specific interaction with the complex of replication protein A and single-stranded DNA. PNAS 95:6049–54 [Google Scholar]
  111. Gibb B, Ye LF, Kwon Y, Niu H, Sung P, Greene EC. 111.  2014. Protein dynamics during presynaptic-complex assembly on individual single-stranded DNA molecules. Nat. Struct. Mol. Biol. 21:893–900 [Google Scholar]
  112. Sasanuma H, Tawaramoto MS, Lao JP, Hosaka H, Sanda E. 112.  et al. 2013. A new protein complex promoting the assembly of Rad51 filaments. Nat. Commun. 4:1676 [Google Scholar]
  113. Fortin GS, Symington LS. 113.  2002. Mutations in yeast Rad51 that partially bypass the requirement for Rad55 and Rad57 in DNA repair by increasing the stability of Rad51–DNA complexes. EMBO J. 21:3160–70 [Google Scholar]
  114. Fung CW, Mozlin AM, Symington LS. 114.  2009. Suppression of the double-strand-break-repair defect of the Saccharomyces cerevisiae rad57 mutant. Genetics 181:1195–206 [Google Scholar]
  115. Liu J, Renault L, Veaute X, Fabre F, Stahlberg H, Heyer WD. 115.  2011. Rad51 paralogues Rad55-Rad57 balance the antirecombinase Srs2 in Rad51 filament formation. Nature 479:245–48 [Google Scholar]
  116. Bernstein KA, Reid RJ, Sunjevaric I, Demuth K, Burgess RC, Rothstein R. 116.  2011. The Shu complex, which contains Rad51 paralogues, promotes DNA repair through inhibition of the Srs2 anti-recombinase. Mol. Biol. Cell 22:1599–607 [Google Scholar]
  117. Shor E, Weinstein J, Rothstein R. 117.  2005. A genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: four genes involved in error-free DNA repair. Genetics 169:1275–89 [Google Scholar]
  118. Gaines WA, Godin SK, Kabbinavar FF, Rao T, VanDemark AP. 118.  et al. 2015. Promotion of presynaptic filament assembly by the ensemble of S. cerevisiae Rad51 paralogues with Rad52. Nat. Commun. 6:7834 [Google Scholar]
  119. Jensen RB, Carreira A, Kowalczykowski SC. 119.  2010. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 467:678–83 [Google Scholar]
  120. Liu J, Doty T, Gibson B, Heyer WD. 120.  2010. Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA. Nat. Struct. Mol. Biol. 17:1260–62 [Google Scholar]
  121. Wong AK, Pero R, Ormonde PA, Tavtigian SV, Bartel PL. 121.  1997. RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J. Biol. Chem. 272:31941–44 [Google Scholar]
  122. Bignell G, Micklem G, Stratton MR, Ashworth A, Wooster R. 122.  1997. The BRC repeats are conserved in mammalian BRCA2 proteins. Hum. Mol. Genet. 6:53–58 [Google Scholar]
  123. Hilario J, Amitani I, Baskin RJ, Kowalczykowski SC. 123.  2009. Direct imaging of human Rad51 nucleoprotein dynamics on individual DNA molecules. PNAS 106:361–68 [Google Scholar]
  124. Rajendra E, Venkitaraman AR. 124.  2010. Two modules in the BRC repeats of BRCA2 mediate structural and functional interactions with the RAD51 recombinase. Nucleic Acids Res. 38:82–96 [Google Scholar]
  125. Carreira A, Hilario J, Amitani I, Baskin RJ, Shivji MK. 125.  et al. 2009. The BRC repeats of BRCA2 modulate the DNA-binding selectivity of RAD51. Cell 136:1032–43 [Google Scholar]
  126. Shivji MK, Mukund SR, Rajendra E, Chen S, Short JM. 126.  et al. 2009. The BRC repeats of human BRCA2 differentially regulate RAD51 binding on single- versus double-stranded DNA to stimulate strand exchange. PNAS 106:13254–59 [Google Scholar]
  127. Carreira A, Kowalczykowski SC. 127.  2011. Two classes of BRC repeats in BRCA2 promote RAD51 nucleoprotein filament function by distinct mechanisms. PNAS 108:10448–53 [Google Scholar]
  128. Shahid T, Soroka J, Kong EH, Malivert L, McIlwraith MJ. 128.  et al. 2014. Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor. Nat. Struct. Mol. Biol. 21:962–68 [Google Scholar]
  129. Reuter M, Zelensky A, Smal I, Meijering E, van Cappellen WA. 129.  et al. 2014. BRCA2 diffuses as oligomeric clusters with RAD51 and changes mobility after DNA damage in live cells. J. Cell Biol. 207:599–613 [Google Scholar]
  130. Zhao W, Vaithiyalingam S, San Filippo J, Maranon DG, Jimenez-Sainz J. 130.  et al. 2015. Promotion of BRCA2-dependent homologous recombination by DSS1 via RPA targeting and DNA mimicry. Mol. Cell 59:176–87 [Google Scholar]
  131. Prakash R, Zhang Y, Feng W, Jasin M. 131.  2015. Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb. Perspect. Biol. 7:a016600 [Google Scholar]
  132. Martinez JS, von Nicolai C, Kim T, Ehlen A, Mazin AV. 132.  et al. 2016. BRCA2 regulates DMC1-mediated recombination through the BRC repeats. PNAS 1133515–20
  133. Haurwitz RE, Jinek M, Wiedenheft B, Zhou K, Doudna JA. 133.  2010. Sequence- and structure-specific RNA processing by a CRISPR endonuclease. Science 329:1355–58 [Google Scholar]
  134. Kowalczykowski SC. 134.  1991. Biochemistry of genetic recombination: energetics and mechanism of DNA strand exchange. Annu. Rev. Biophys. Biophys. Chem. 20:539–75 [Google Scholar]
  135. Kowalczykowski SC. 135.  1991. Biochemical and biological function of Escherichia coli RecA protein: behavior of mutant RecA proteins. Biochimie 73:289–304 [Google Scholar]
  136. Chen Z, Yang H, Pavletich NP. 136.  2008. Mechanism of homologous recombination from the RecA–ssDNA/dsDNA structures. Nature 453:489–94 [Google Scholar]
  137. Kowalczykowski SC. 137.  2008. Structural biology: snapshots of DNA repair. Nature 453:463–66 [Google Scholar]
  138. Mazin AV, Kowalczykowski SC. 138.  1996. The specificity of the secondary DNA binding site of RecA protein defines its role in DNA strand exchange. PNAS 93:10673–78 [Google Scholar]
  139. Forget AL, Kowalczykowski SC. 139.  2012. Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search. Nature 482:423–27 [Google Scholar]
  140. Berg OG, Winter RB, von Hippel PH. 140.  1981. Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory. Biochemistry 20:6929–48 [Google Scholar]
  141. Ragunathan K, Joo C, Ha T. 141.  2011. Real-time observation of strand exchange reaction with high spatiotemporal resolution. Structure 19:1064–73 [Google Scholar]
  142. Ragunathan K, Liu C, Ha T. 142.  2012. RecA filament sliding on DNA facilitates homology search. eLife 1:e00067 [Google Scholar]
  143. Saladin A, Amourda C, Poulain P, Ferey N, Baaden M. 143.  et al. 2010. Modeling the early stage of DNA sequence recognition within RecA nucleoprotein filaments. Nucleic Acids Res. 38:6313–23 [Google Scholar]
  144. Savir Y, Tlusty T. 144.  2010. RecA-mediated homology search as a nearly optimal signal detection system. Mol. Cell 40:388–96 [Google Scholar]
  145. Danilowicz C, Yang D, Kelley C, Prevost C, Prentiss M. 145.  2015. The poor homology stringency in the heteroduplex allows strand exchange to incorporate desirable mismatches without sacrificing recognition in vivo. Nucleic Acids Res. 43:6473–85 [Google Scholar]
  146. Qi Z, Redding S, Lee JY, Gibb B, Kwon Y. 146.  et al. 2015. DNA sequence alignment by microhomology sampling during homologous recombination. Cell 160:856–69 [Google Scholar]
  147. Lesterlin C, Ball G, Schermelleh L, Sherratt DJ. 147.  2014. RecA bundles mediate homology pairing between distant sisters during DNA break repair. Nature 506:249–53 [Google Scholar]
  148. Yu X, West SC, Egelman EH. 148.  1997. Structure and subunit composition of the RuvAB–Holliday junction complex. J. Mol. Biol. 266:217–22 [Google Scholar]
  149. Dawid A, Croquette V, Grigoriev M, Heslot F. 149.  2004. Single-molecule study of RuvAB-mediated Holliday-junction migration. PNAS 101:11611–16 [Google Scholar]
  150. Wu L, Davies SL, Levitt NC, Hickson ID. 150.  2001. Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. J. Biol. Chem. 276:19375–81 [Google Scholar]
  151. Hickson ID. 151.  2003. RecQ helicases: caretakers of the genome. Nat. Rev. Cancer 3:169–78 [Google Scholar]
  152. Bianco PR, Tracy RB, Kowalczykowski SC. 152.  1998. DNA strand exchange proteins: a biochemical and physical comparison. Front. Biosci. 3:D570–603 [Google Scholar]
  153. Bugreev DV, Mazin AV. 153.  2004. Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity. PNAS 101:9988–93 [Google Scholar]
  154. Tombline G, Shim KS, Fishel R. 154.  2002. Biochemical characterization of the human RAD51 protein. II. Adenosine nucleotide binding and competition. J. Biol. Chem. 277:14426–33 [Google Scholar]
  155. Shim KS, Schmutte C, Tombline G, Heinen CD, Fishel R. 155.  2004. hXRCC2 enhances ADP/ATP processing and strand exchange by hRAD51. J. Biol. Chem. 279:30385–94 [Google Scholar]
  156. Sung P, Robberson DL. 156.  1995. DNA strand exchange mediated by a RAD51–ssDNA nucleoprotein filament with polarity opposite to that of RecA. Cell 82:453–61 [Google Scholar]
  157. Szekvolgyi L, Ohta K, Nicolas A. 157.  2015. Initiation of meiotic homologous recombination: flexibility, impact of histone modifications, and chromatin remodeling. Cold Spring Harb. Perspect. Biol. 7:a016527 [Google Scholar]
  158. Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A. 158.  et al. 1993–2015. GeneReviews Seattle, WA: Univ. Wash http://www.ncbi.nlm.nih.gov/books/NBK1116/
  159. Wang AT, Kim T, Wagner JE, Conti BA, Lach FP. 159.  et al. 2015. A dominant mutation in human RAD51 reveals its function in DNA interstrand crosslink repair independent of homologous recombination. Mol. Cell 59:478–90 [Google Scholar]
  160. Alter BP, Kupfer G. 160.  Fanconi anemia; 2002. See Ref. 158, http://www.ncbi.nlm.nih.gov/books/NBK1401/, updated Feb. 7, 2013
  161. Sanz MM, German J. 161.  Bloom's syndrome; 2006. See Ref. 158, http://www.ncbi.nlm.nih.gov/books/NBK1398/, updated Mar. 28, 2013
  162. Varon R, Demuth I, Digweed M. 162.  Nijmegen breakage syndrome; 1999. See Ref. 158, http://www.ncbi.nlm.nih.gov/books/NBK1176/, updated May 8, 2014
  163. Petrucelli N, Daly MB, Feldman GL. 163.  BRCA1 and BRCA2 hereditary breast and ovarian cancer; 1998. See Ref. 158, http://www.ncbi.nlm.nih.gov/books/NBK1247/, updated Sep. 26, 2013
  164. Cybulski C, Carrot-Zhang J, Kluzniak W, Rivera B, Kashyap A. 164.  et al. 2015. Germline RECQL mutations are associated with breast cancer susceptibility. Nat. Genet. 47:643–46 [Google Scholar]
  165. Sun J, Wang Y, Xia Y, Xu Y, Ouyang T. 165.  et al. 2015. Mutations in RECQL gene are associated with predisposition to breast cancer. PLOS Genet. 11:e1005228 [Google Scholar]
  166. Oshima J, Martin GM, Hisama FM. 166.  Werner syndrome; 2002. See Ref. 158, http://www.ncbi.nlm.nih.gov/books/NBK1514/, updated Mar. 27, 2014
  167. Croteau DL, Popuri V, Opresko PL, Bohr VA. 167.  2014. Human RecQ helicases in DNA repair, recombination, and replication. Annu. Rev. Biochem. 83:519–52 [Google Scholar]
  168. 168. Gatti R. Ataxia–telangiectasia 1999. See Ref. 158, http://www.ncbi.nlm.nih.gov/books/NBK26468/, updated Mar. 11, 2010
  169. Wang LL, Plon SE. 169.  Rothmund–Thomson syndrome; 1999. See Ref. 158, http://www.ncbi.nlm.nih.gov/books/NBK1237/, updated June 6, 2013
  170. Harmon FG, Brockman JP, Kowalczykowski SC. 170.  2003. RecQ helicase stimulates both DNA catenation and changes in DNA topology by topoisomerase II. J. Biol. Chem. 278:42668–78 [Google Scholar]
  171. Galletto RG, Kowalczykowski SC. 171.  2007. RecA. Curr. Biol. 17:R395–97 [Google Scholar]
/content/journals/10.1146/annurev-biochem-060614-034352
Loading
/content/journals/10.1146/annurev-biochem-060614-034352
Loading

Data & Media loading...

  • Article Type: Review Article
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