Writers, readers, and erasers of histone ubiquitylation in DNA double-strand break repair

Frontiers in Genetics

Volumn 7, Issue JUN, 2016, Pages

  Smeenk, Godelieve ^a   Mailand, Niels ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Chromatin; DNA damage response; DNA double strand breaks; DNA repair; Histones; Ubiquitin

Indexed keywords

CYTOTOXIC AGENT; DOUBLE STRANDED DNA; HISTONE; RING FINGER PROTEIN; UBIQUITIN; UBIQUITIN PROTEIN LIGASE;

CELL CYCLE; CHROMATIN; DNA DAMAGE; DNA REPAIR; DNA STRAND BREAKAGE; GENE DISRUPTION; GENE INSERTION; GENOME; GENOMIC INSTABILITY; HISTONE CODE; HISTONE UBIQUITINATION; HUMAN; HUMAN EXPERIMENT; IMMUNE DEFICIENCY; NERVE DEGENERATION; RADIOSENSITIVITY; REVIEW;

EID: 84977519218     PISSN: None     EISSN: 16648021     Source Type: Journal    
DOI: 10.3389/fgene.2016.00122     Document Type: Review

References (156)

1. Acs, K., Luijsterburg, M. S., Ackermann, L., Salomons, F. A., Hoppe, T., and Dantuma, N. P. (2011). The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks. Nat. Struct. Mol. Biol. 18, 1345-1350. doi: 10.1038/nsmb.2188
2. Alt, F. W., Zhang, Y., Meng, F. L., Guo, C., and Schwer, B. (2013). Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell 152, 417-429. doi: 10.1016/j.cell.2013.01.007
3. Barnes, D. E., and Lindahl, T. (2004). Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu. Rev. Genet. 38, 445-476. doi: 10.1146/annurev.genet.38.072902.092448
4. Bekker-Jensen, S., and Mailand, N. (2010). Assembly and function of DNA double-strand break repair foci in mammalian cells. DNA Repair (Amst). 9, 1219-1228. doi: 10.1016/j.dnarep.2010.09.010
5. Bekker-Jensen, S., Rendtlew Danielsen, J., Fugger, K., Gromova, I., Nerstedt, A., Lukas, C., et al. (2010). HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat. Cell Biol. 12, 80-86. doi: 10.1038/ncb2008
6. Boersma, V., Moatti, N., Segura-Bayona, S., Peuscher, M. H., van der Torre, J., Wevers, B. A., et al. (2015). MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5' end resection. Nature 521, 537-540. doi: 10.1038/nature14216
7. Bohgaki, M., Bohgaki, T., El Ghamrasni, S., Srikumar, T., Maire, G., Panier, S., et al. (2013). RNF168 ubiquitylates 53BP1 and controls its response to DNA double-strand breaks. Proc. Natl. Acad. Sci. U.S.A. 110, 20982-20987. doi: 10.1073/pnas.1320302111
8. Botuyan, M. V., Lee, J., Ward, I. M., Kim, J. E., Thompson, J. R., Chen, J., et al. (2006). Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127, 1361-1373. doi: 10.1016/j.cell.2006.10.043
9. Bouwman, P., Aly, A., Escandell, J. M., Pieterse, M., Bartkova, J., van der Gulden, H., et al. (2010). 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol. 17, 688-695. doi: 10.1038/nsmb.1831
10. Briggs, S. D., Xiao, T., Sun, Z. W., Caldwell, J. A., Shabanowitz, J., Hunt, D. F., et al. (2002). Gene silencing: trans-histone regulatory pathway in chromatin. Nature 418, 498. doi: 10.1038/nature00970
11. Bunting, S. F., Callén, E., Wong, N., Chen, H. T., Polato, F., Gunn, A., et al. (2010). 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141, 243-254. doi: 10.1016/j.cell.2010.03.012
12. Butler, L. R., Densham, R. M., Jia, J., Garvin, A. J., Stone, H. R., Shah, V., et al. (2012). The proteasomal de-ubiquitinating enzyme POH1 promotes the double-strand DNA break response. EMBO J. 31, 3918-3934. doi: 10.1038/emboj.2012.232
13. Cai, S. Y., Babbitt, R. W., and Marchesi, V. T. (1999). A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division. Proc. Natl. Acad. Sci. U.S.A. 96, 2828-2833. doi: 10.1073/pnas.96.6.2828
14. Callen, E., Di Virgilio, M., Kruhlak, M. J., Nieto-Soler, M., Wong, N., Chen, H. T., et al. (2013). 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell 153, 1266-1280. doi: 10.1016/j.cell.2013.05.023
15. Cao, L., Xu, X., Bunting, S. F., Liu, J., Wang, R. H., Cao, L. L., et al. (2009). A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Mol. Cell 35, 534-541. doi: 10.1016/j.molcel.2009.06.037
16. Ceccaldi, R., Rondinelli, B., and D'andrea, A. D. (2016). Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 26, 52-64. doi: 10.1016/j.tcb.2015.07.009
17. Chapman, J. R., Barral, P., Vannier, J. B., Borel, V., Steger, M., Tomas-Loba, A., et al. (2013). RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection. Mol. Cell 49, 858-871. doi: 10.1016/j.molcel.2013.01.002
18. Chapman, J. R., Sossick, A. J., Boulton, S. J., and Jackson, S. P. (2012a). BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair. J. Cell Sci. 125, 3529-3534. doi: 10.1242/jcs.105353
19. Chapman, J. R., Taylor, M. R., and Boulton, S. J. (2012b). Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 47, 497-510. doi: 10.1016/j.molcel.2012.07.029
20. Chen, J., Feng, W., Jiang, J., Deng, Y., and Huen, M. S. (2012). Ring finger protein RNF169 antagonizes the ubiquitin-dependent signaling cascade at sites of DNA damage. J. Biol. Chem. 287, 27715-27722. doi: 10.1074/jbc. M112.373530
21. Chou, D. M., Adamson, B., Dephoure, N. E., Tan, X., Nottke, A. C., Hurov, K. E., et al. (2010). A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage. Proc. Natl. Acad. Sci. U.S.A. 107, 18475-18480. doi: 10.1073/pnas.1012946107
22. Ciccia, A., and Elledge, S. J. (2010). The DNA damage response: making it safe to play with knives. Mol. Cell 40, 179-204. doi: 10.1016/j.molcel.2010.09.019
23. Coleman, K. A., and Greenberg, R. A. (2011). The BRCA1-RAP80 complex regulates DNA repair mechanism utilization by restricting end resection. J. Biol. Chem. 286, 13669-13680. doi: 10.1074/jbc. M110.213728
24. Cullinan, S. B., Gordan, J. D., Jin, J., Harper, J. W., and Diehl, J. A. (2004). The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Mol. Cell. Biol. 24, 8477-8486. doi: 10.1128/MCB.24.19.8477-8486.2004
25. De Massy, B. (2013). Initiation of meiotic recombination: how and where? Conservation and specificities among eukaryotes. Annu. Rev. Genet. 47, 563-599. doi: 10.1146/annurev-genet-110711-155423
26. Devgan, S. S., Sanal, O., Doil, C., Nakamura, K., Nahas, S. A., Pettijohn, K., et al. (2011). Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia. Cell Death Differ. 18, 1500-1506. doi: 10.1038/cdd.2011.18
27. Dikic, I., Wakatsuki, S., and Walters, K. J. (2009). Ubiquitin-binding domains-from structures to functions. Nat. Rev. Mol. Cell Biol. 10, 659-671. doi: 10.1038/nrm2767
28. Di Virgilio, M., Callen, E., Yamane, A., Zhang, W., Jankovic, M., Gitlin, A. D., et al. (2013). Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339, 711-715. doi: 10.1126/science.1230624
29. Doil, C., Mailand, N., Bekker-Jensen, S., Menard, P., Larsen, D. H., Pepperkok, R., et al. (2009). RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 136, 435-446. doi: 10.1016/j.cell.2008.12.041
30. Dulev, S., Tkach, J., Lin, S., and Batada, N. N. (2014). SET8 methyltransferase activity during the DNA double-strand break response is required for recruitment of 53BP1. EMBO Rep. 15, 1163-1174. doi: 10.15252/embr.201439434
31. Escribano-Díaz, C., Orthwein, A., Fradet-Turcotte, A., Xing, M., Young, J. T., Tkac, J., et al. (2013). A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol. Cell 49, 872-883. doi: 10.1016/j.molcel.2013.01.001
32. Facchino, S., Abdouh, M., Chatoo, W., and Bernier, G. (2010). BMI1 confers radioresistance to normal and cancerous neural stem cells through recruitment of the DNA damage response machinery. J. Neurosci. 30, 10096-10111. doi: 10.1523/JNEUROSCI.1634-10.2010
33. Feng, L., Fong, K. W., Wang, J., Wang, W., and Chen, J. (2013). RIF1 counteracts BRCA1-mediated end resection during DNA repair. J. Biol. Chem. 288, 11135-11143. doi: 10.1074/jbc. M113.457440
34. Fierz, B., Chatterjee, C., McGinty, R. K., Bar-Dagan, M., Raleigh, D. P., and Muir, T. W. (2011). Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction. Nat. Chem. Biol. 7, 113-119. doi: 10.1038/nchembio.501
35. Fradet-Turcotte, A., Canny, M. D., Escribano-Díaz, C., Orthwein, A., Leung, C. C., Huang, H., et al. (2013). 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature 499, 50-54. doi: 10.1038/nature12318
36. Fuchs, G., Shema, E., Vesterman, R., Kotler, E., Wolchinsky, Z., Wilder, S., et al. (2012). RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation. Mol. Cell 46, 662-673. doi: 10.1016/j.molcel.2012.05.023
37. Galanty, Y., Belotserkovskaya, R., Coates, J., and Jackson, S. P. (2012). RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair. Genes Dev. 26, 1179-1195. doi: 10.1101/gad.188284.112
38. Galanty, Y., Belotserkovskaya, R., Coates, J., Polo, S., Miller, K. M., and Jackson, S. P. (2009). Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 462, 935-939. doi: 10.1038/nature08657
39. Gatti, M., Pinato, S., Maiolica, A., Rocchio, F., Prato, M. G., Aebersold, R., et al. (2015). RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage. Cell Rep. 10, 226-238. doi: 10.1016/j.celrep.2014.12.021
40. Gatti, M., Pinato, S., Maspero, E., Soffientini, P., Polo, S., and Penengo, L. (2012). A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase. Cell Cycle 11, 2538-2544. doi: 10.4161/cc.20919
41. Ginjala, V., Nacerddine, K., Kulkarni, A., Oza, J., Hill, S. J., Yao, M., et al. (2011). BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair. Mol. Cell. Biol. 31, 1972-1982. doi: 10.1128/MCB.00981-10
42. Gudjonsson, T., Altmeyer, M., Savic, V., Toledo, L., Dinant, C., Grofte, M., et al. (2012). TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. Cell 150, 697-709. doi: 10.1016/j.cell.2012.06.039
43. Harding, S. M., Boiarsky, J. A., and Greenberg, R. A. (2015). ATM dependent silencing links nucleolar chromatin reorganization to DNA damage recognition. Cell Rep. 13, 251-259. doi: 10.1016/j.celrep.2015.08.085
44. Harshman, S. W., Young, N. L., Parthun, M. R., and Freitas, M. A. (2013). H1 histones: current perspectives and challenges. Nucleic Acids Res. 41, 9593-9609. doi: 10.1093/nar/gkt700
45. Hartlerode, A. J., Guan, Y., Rajendran, A., Ura, K., Schotta, G., Xie, A., et al. (2012). Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks. PLoS ONE 7:e49211. doi: 10.1371/journal.pone.0049211
46. Henry, K. W., Wyce, A., Lo, W. S., Duggan, L. J., Emre, N. C., Kao, C. F., et al. (2003). Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes Dev. 17, 2648-2663. doi: 10.1101/gad.1144003
47. Heyer, W. D., Ehmsen, K. T., and Liu, J. (2010). Regulation of homologous recombination in eukaryotes. Annu. Rev. Genet. 44, 113-139. doi: 10.1146/annurev-genet-051710-150955
48. Hofmann, R. M., and Pickart, C. M. (1999). Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96, 645-653. doi: 10.1016/S0092-8674(00)80575-9
49. Hondele, M., Stuwe, T., Hassler, M., Halbach, F., Bowman, A., Zhang, E. T., et al. (2013). Structural basis of histone H2A-H2B recognition by the essential chaperone FACT. Nature 499, 111-114. doi: 10.1038/nature12242
50. Hsiao, K. Y., and Mizzen, C. A. (2013). Histone H4 deacetylation facilitates 53BP1 DNA damage signaling and double-strand break repair. J. Mol. Cell Biol. 5, 157-165. doi: 10.1093/jmcb/mjs066
51. Hu, Y., Scully, R., Sobhian, B., Xie, A., Shestakova, E., and Livingston, D. M. (2011). RAP80-directed tuning of BRCA1 homologous recombination function at ionizing radiation-induced nuclear foci. Genes Dev. 25, 685-700. doi: 10.1101/gad.2011011
52. Huang, J., Huen, M. S., Kim, H., Leung, C. C., Glover, J. N., Yu, X., et al. (2009). RAD18 transmits DNA damage signalling to elicit homologous recombination repair. Nat. Cell Biol. 11, 592-603. doi: 10.1038/ncb1865
53. Huen, M. S., Grant, R., Manke, I., Minn, K., Yu, X., Yaffe, M. B., et al. (2007). RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131, 901-914. doi: 10.1016/j.cell.2007.09.041
54. Huen, M. S., Sy, S. M., and Chen, J. (2010). BRCA1 and its toolbox for the maintenance of genome integrity. Nat. Rev. Mol. Cell Biol. 11, 138-148. doi: 10.1038/nrm2831
55. Ismail, I. H., Andrin, C., McDonald, D., and Hendzel, M. J. (2010). BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair. J. Cell Biol. 191, 45-60. doi: 10.1083/jcb.201003034
56. Ismail, I. H., Gagné, J. P., Genois, M. M., Strickfaden, H., McDonald, D., Xu, Z., et al. (2015). The RNF138 E3 ligase displaces Ku to promote DNA end resection and regulate DNA repair pathway choice. Nat. Cell Biol. 17, 1446-1457. doi: 10.1038/ncb3259
57. Jackson, S. P., and Bartek, J. (2009). The DNA-damage response in human biology and disease. Nature 461, 1071-1078. doi: 10.1038/nature08467
58. Jason, L. J., Moore, S. C., Ausio, J., and Lindsey, G. (2001). Magnesium-dependent association and folding of oligonucleosomes reconstituted with ubiquitinated H2A. J. Biol. Chem. 276, 14597-14601. doi: 10.1074/jbc. M011153200
59. Joo, H. Y., Zhai, L., Yang, C., Nie, S., Erdjument-Bromage, H., Tempst, P., et al. (2007). Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature 449, 1068-1072. doi: 10.1038/nature06256
60. Juang, Y. C., Landry, M. C., Sanches, M., Vittal, V., Leung, C. C., Ceccarelli, D. F., et al. (2012). OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme function. Mol. Cell 45, 384-397. doi: 10.1016/j.molcel.2012.01.011
61. Kaidi, A., and Jackson, S. P. (2013). KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling. Nature 498, 70-74. doi: 10.1038/nature12201
62. Kakarougkas, A., Ismail, A., Chambers, A. L., Riballo, E., Herbert, A. D., Kunzel, J., et al. (2014). Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin. Mol. Cell 55, 723-732. doi: 10.1016/j.molcel.2014.06.028
63. Kakarougkas, A., Ismail, A., Katsuki, Y., Freire, R., Shibata, A., and Jeggo, P. A. (2013). Co-operation of BRCA1 and POH1 relieves the barriers posed by 53BP1 and RAP80 to resection. Nucleic Acids Res. 41, 10298-10311. doi: 10.1093/nar/gkt802
64. Kalb, R., Mallery, D. L., Larkin, C., Huang, J. T., and Hiom, K. (2014). BRCA1 is a histone-H2A-specific ubiquitin ligase. Cell Rep. 8, 999-1005. doi: 10.1016/j.celrep.2014.07.025
65. Karanam, K., Kafri, R., Loewer, A., and Lahav, G. (2012). Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and a maximal use of HR in mid S phase. Mol. Cell 47, 320-329. doi: 10.1016/j.molcel.2012.05.052
66. Kato, K., Nakajima, K., Ui, A., Muto-Terao, Y., Ogiwara, H., and Nakada, S. (2014). Fine-tuning of DNA damage-dependent ubiquitination by OTUB2 supports the DNA repair pathway choice. Mol. Cell 53, 617-630. doi: 10.1016/j.molcel.2014.01.030
67. Kim, H., Chen, J., and Yu, X. (2007). Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316, 1202-1205. doi: 10.1126/science.1139621
68. Kim, J., Guermah, M., McGinty, R. K., Lee, J. S., Tang, Z., Milne, T. A., et al. (2009). RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell 137, 459-471. doi: 10.1016/j.cell.2009.02.027
69. Kobayashi, A., Kang, M. I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., et al. (2004). Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 24, 7130-7139. doi: 10.1128/MCB.24.16.7130-7139.2004
70. Kolas, N. K., Chapman, J. R., Nakada, S., Ylanko, J., Chahwan, R., Sweeney, F. D., et al. (2007). Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318, 1637-1640. doi: 10.1126/science.1150034
71. Kruhlak, M., Crouch, E. E., Orlov, M., Montaño, C., Gorski, S. A., Nussenzweig, A., et al. (2007). The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaks. Nature 447, 730-734. doi: 10.1038/nature05842
72. Lancini, C., van den Berk, P. C., Vissers, J. H., Gargiulo, G., Song, J. Y., Hulsman, D., et al. (2014). Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells. J. Exp. Med. 211, 1759-1777. doi: 10.1084/jem.20131436
73. Larsen, D. H., Hari, F., Clapperton, J. A., Gwerder, M., Gutsche, K., Altmeyer, M., et al. (2014). The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage. Nat. Cell Biol. 16, 792-803. doi: 10.1038/ncb3007
74. Leung, J. W., Agarwal, P., Canny, M. D., Gong, F., Robison, A. D., Finkelstein, I. J., et al. (2014). Nucleosome acidic patch promotes RNF168-and RING1B/BMI1-dependent H2AX and H2A ubiquitination and DNA damage signaling. PLoS Genet. 10:e1004178. doi: 10.1371/journal.pgen.1004178
75. Lieber, M. R. (2010). The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu. Rev. Biochem. 79, 181-211. doi: 10.1146/annurev.biochem.052308.093131
76. Lukas, J., Lukas, C., and Bartek, J. (2011). More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat. Cell Biol. 13, 1161-1169. doi: 10.1038/ncb2344
77. Mailand, N., Bekker-Jensen, S., Faustrup, H., Melander, F., Bartek, J., Lukas, C., et al. (2007). RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131, 887-900. doi: 10.1016/j.cell.2007.09.040
78. Mailand, N., Gibbs-Seymour, I., and Bekker-Jensen, S. (2013). Regulation of PCNA-protein interactions for genome stability. Nat. Rev. Mol. Cell Biol. 14, 269-282. doi: 10.1038/nrm3562
79. Mallette, F. A., Mattiroli, F., Cui, G., Young, L. C., Hendzel, M. J., Mer, G., et al. (2012). RNF8-and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites. EMBO J. 31, 1865-1878. doi: 10.1038/emboj.2012.47
80. Mattiroli, F., Uckelmann, M., Sahtoe, D. D., Van Dijk, W. J., and Sixma, T. K. (2014). The nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A. Nat. Commun. 5, 3291. doi: 10.1038/ncomms4291
81. Mattiroli, F., Vissers, J. H., van Dijk, W. J., Ikpa, P., Citterio, E., Vermeulen, W., et al. (2012). RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell 150, 1182-1195. doi: 10.1016/j.cell.2012.08.005
82. Maxwell, K. N., and Domchek, S. M. (2012). Cancer treatment according to BRCA1 and BRCA2 mutations. Nat. Rev. Clin. Oncol. 9, 520-528. doi: 10.1038/nrclinonc.2012.123
83. Mermershtain, I., and Glover, J. N. (2013). Structural mechanisms underlying signaling in the cellular response to DNA double strand breaks. Mutat. Res. 750, 15-22. doi: 10.1016/j.mrfmmm.2013.07.004
84. Morris, J. R., and Solomon, E. (2004). BRCA1: BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Hum. Mol. Genet. 13, 807-817. doi: 10.1093/hmg/ddh095
85. Mosbech, A., Lukas, C., Bekker-Jensen, S., and Mailand, N. (2013). The deubiquitylating enzyme USP44 counteracts the DNA double-strand break response mediated by the RNF8 and RNF168 ubiquitin ligases. J. Biol. Chem. 288, 16579-16587. doi: 10.1074/jbc. M113.459917
86. Moyal, L., Lerenthal, Y., Gana-Weisz, M., Mass, G., So, S., Wang, S. Y., et al. (2011). Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Mol. Cell 41, 529-542. doi: 10.1016/j.molcel.2011.02.015
87. Munoz, I. M., Jowsey, P. A., Toth, R., and Rouse, J. (2007). Phospho-epitope binding by the BRCT domains of hPTIP controls multiple aspects of the cellular response to DNA damage. Nucleic Acids Res. 35, 5312-5322. doi: 10.1093/nar/gkm493
88. Muñoz, M. C., Laulier, C., Gunn, A., Cheng, A., Robbiani, D. F., Nussenzweig, A., et al. (2012). RING finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1. J. Biol. Chem. 287, 40618-40628. doi: 10.1074/jbc. M112.410951
89. Muñoz, M. C., Yanez, D. A., and Stark, J. M. (2014). An RNF168 fragment defective for focal accumulation at DNA damage is proficient for inhibition of homologous recombination in BRCA1 deficient cells. Nucleic Acids Res. 42, 7720-7733. doi: 10.1093/nar/gku421
90. Murga, M., Jaco, I., Fan, Y., Soria, R., Martinez-Pastor, B., Cuadrado, M., et al. (2007). Global chromatin compaction limits the strength of the DNA damage response. J. Cell Biol. 178, 1101-1108. doi: 10.1083/jcb.200704140
91. Nakada, S., Tai, I., Panier, S., Al-Hakim, A., Iemura, S., Juang, Y. C., et al. (2010). Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1. Nature 466, 941-946. doi: 10.1038/nature09297
92. Nakamura, K., Kato, A., Kobayashi, J., Yanagihara, H., Sakamoto, S., Oliveira, D. V., et al. (2011). Regulation of homologous recombination by RNF20-dependent H2B ubiquitination. Mol. Cell 41, 515-528. doi: 10.1016/j.molcel.2011.02.002
93. Ng, H. H., Xu, R. M., Zhang, Y., and Struhl, K. (2002). Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J. Biol. Chem. 277, 34655-34657. doi: 10.1074/jbc. C200433200
94. Nicassio, F., Corrado, N., Vissers, J. H., Areces, L. B., Bergink, S., Marteijn, J. A., et al. (2007). Human USP3 is a chromatin modifier required for S phase progression and genome stability. Curr. Biol. 17, 1972-1977. doi: 10.1016/j.cub.2007.10.034
95. Nishioka, K., Rice, J. C., Sarma, K., Erdjument-Bromage, H., Werner, J., Wang, Y., et al. (2002). PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol. Cell 9, 1201-1213. doi: 10.1016/S1097-2765(02)00548-8
96. Oda, H., Hübner, M. R., Beck, D. B., Vermeulen, M., Hurwitz, J., Spector, D. L., et al. (2010). Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage. Mol. Cell 40, 364-376. doi: 10.1016/j.molcel.2010.10.011
97. Okamoto, K., Bartocci, C., Ouzounov, I., Diedrich, J. K., Yates, J. R. III., and Denchi, E. L. (2013). A two-step mechanism for TRF2-mediated chromosome-end protection. Nature 494, 502-505. doi: 10.1038/nature11873
98. Oliveira, D. V., Kato, A., Nakamura, K., Ikura, T., Okada, M., Kobayashi, J., et al. (2014). Histone chaperone FACT regulates homologous recombination by chromatin remodeling through interaction with RNF20. J. Cell Sci. 127, 763-772. doi: 10.1242/jcs.135855
99. Orthwein, A., Fradet-Turcotte, A., Noordermeer, S. M., Canny, M. D., Brun, C. M., Strecker, J., et al. (2014). Mitosis inhibits DNA double-strand break repair to guard against telomere fusions. Science 344, 189-193. doi: 10.1126/science.1248024
100. Orthwein, A., Noordermeer, S. M., Wilson, M. D., Landry, S., Enchev, R. I., Sherker, A., et al. (2015). A mechanism for the suppression of homologous recombination in G1 cells. Nature 528, 422-426. doi: 10.1038/nature16142
101. Pan, M. R., Peng, G., Hung, W. C., and Lin, S. Y. (2011). Monoubiquitination of H2AX protein regulates DNA damage response signaling. J. Biol. Chem. 286, 28599-28607. doi: 10.1074/jbc. M111.256297
102. Panier, S., Ichijima, Y., Fradet-Turcotte, A., Leung, C. C., Kaustov, L., Arrowsmith, C. H., et al. (2012). Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks. Mol. Cell 47, 383-395. doi: 10.1016/j.molcel.2012.05.045
103. Pavri, R., Zhu, B., Li, G., Trojer, P., Mandal, S., Shilatifard, A., et al. (2006). Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell 125, 703-717. doi: 10.1016/j.cell.2006.04.029
104. Pei, H., Zhang, L., Luo, K., Qin, Y., Chesi, M., Fei, F., et al. (2011). MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites. Nature 470, 124-128. doi: 10.1038/nature09658
105. Peuscher, M. H., and Jacobs, J. J. (2011). DNA-damage response and repair activities at uncapped telomeres depend on RNF8. Nat. Cell Biol. 13, 1139-1145. doi: 10.1038/ncb2326
106. Pinato, S., Scandiuzzi, C., Arnaudo, N., Citterio, E., Gaudino, G., and Penengo, L. (2009). RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX. BMC Mol. Biol. 10:55. doi: 10.1186/1471-2199-10-55
107. Polanowska, J., Martin, J. S., Garcia-Muse, T., Petalcorin, M. I., and Boulton, S. J. (2006). A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage sites. EMBO J. 25, 2178-2188. doi: 10.1038/sj.emboj.7601102
108. Polo, S. E., and Jackson, S. P. (2011). Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 25, 409-433. doi: 10.1101/gad.2021311
109. Poulsen, M., Lukas, C., Lukas, J., Bekker-Jensen, S., and Mailand, N. (2012). Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks. J. Cell Biol. 197, 189-199. doi: 10.1083/jcb.201109100
110. Raschle, M., Smeenk, G., Hansen, R. K., Temu, T., Oka, Y., Hein, M. Y., et al. (2015). Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. Science 348:1253671. doi: 10.1126/science.1253671
111. Reid, L. J., Shakya, R., Modi, A. P., Lokshin, M., Cheng, J. T., Jasin, M., et al. (2008). E3 ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks. Proc. Natl. Acad. Sci. U.S.A. 105, 20876-20881. doi: 10.1073/pnas.0811203106
112. Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., and Bonner, W. M. (1998). DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273, 5858-5868. doi: 10.1074/jbc.273.10.5858
113. Sato, Y., Yamagata, A., Goto-Ito, S., Kubota, K., Miyamoto, R., Nakada, S., et al. (2012). Molecular basis of Lys-63-linked polyubiquitination inhibition by the interaction between human deubiquitinating enzyme OTUB1 and ubiquitin-conjugating enzyme UBC13. J. Biol. Chem. 287, 25860-25868. doi: 10.1074/jbc. M112.364752
114. Sato, Y., Yoshikawa, A., Mimura, H., Yamashita, M., Yamagata, A., and Fukai, S. (2009). Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80. EMBO J. 28, 2461-2468. doi: 10.1038/emboj.2009.160
115. Schmidt, C. K., Galanty, Y., Sczaniecka-Clift, M., Coates, J., Jhujh, S., Demir, M., et al. (2015). Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair. Nat. Cell Biol. 17, 1458-1470. doi: 10.1038/ncb3260
116. Schoenfeld, A. R., Apgar, S., Dolios, G., Wang, R., and Aaronson, S. A. (2004). BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. Mol. Cell. Biol. 24, 7444-7455. doi: 10.1128/MCB.24.17.7444-7455.2004
117. Schotta, G., Lachner, M., Sarma, K., Ebert, A., Sengupta, R., Reuter, G., et al. (2004). A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 18, 1251-1262. doi: 10.1101/gad.300704
118. Schwertman, P., Bekker-Jensen, S., and Mailand, N. (2016). Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers. Nat. Rev. Mol. Cell Biol. 17, 379-394. doi: 10.1038/nrm.2016.58
119. Shakya, R., Reid, L. J., Reczek, C. R., Cole, F., Egli, D., Lin, C. S., et al. (2011). BRCA1 tumor suppression depends on BRCT phosphoprotein binding, but not its E3 ligase activity. Science 334, 525-528. doi: 10.1126/science.1209909
120. Shanbhag, N. M., Rafalska-Metcalf, I. U., Balane-Bolivar, C., Janicki, S. M., and Greenberg, R. A. (2010). ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell 141, 970-981. doi: 10.1016/j.cell.2010.04.038
121. Shao, G., Lilli, D. R., Patterson-Fortin, J., Coleman, K. A., Morrissey, D. E., and Greenberg, R. A. (2009). The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc. Natl. Acad. Sci. U.S.A. 106, 3166-3171. doi: 10.1073/pnas.0807485106
122. Shibata, A., Conrad, S., Birraux, J., Geuting, V., Barton, O., Ismail, A., et al. (2011). Factors determining DNA double-strand break repair pathway choice in G2 phase. EMBO J. 30, 1079-1092. doi: 10.1038/emboj.2011.27
123. Sims, J. J., and Cohen, R. E. (2009). Linkage-specific avidity defines the lysine 63-linked polyubiquitin-binding preference of rap80. Mol. Cell 33, 775-783. doi: 10.1016/j.molcel.2009.02.011
124. Sobhian, B., Shao, G., Lilli, D. R., Culhane, A. C., Moreau, L. A., Xia, B., et al. (2007). RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316, 1198-1202. doi: 10.1126/science.1139516
125. Stewart, G. S., Panier, S., Townsend, K., Al-Hakim, A. K., Kolas, N. K., Miller, E. S., et al. (2009). The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell 136, 420-434. doi: 10.1016/j.cell.2008.12.042
126. Stewart, G. S., Stankovic, T., Byrd, P. J., Wechsler, T., Miller, E. S., Huissoon, A., et al. (2007). RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling. Proc. Natl. Acad. Sci. U.S.A. 104, 16910-16915. doi: 10.1073/pnas.0708408104
127. Stucki, M., Clapperton, J. A., Mohammad, D., Yaffe, M. B., Smerdon, S. J., and Jackson, S. P. (2005). MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123, 1213-1226. doi: 10.1016/j.cell.2005.09.038
128. Sun, Y., Jiang, X., Xu, Y., Ayrapetov, M. K., Moreau, L. A., Whetstine, J. R., et al. (2009). Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat. Cell Biol. 11, 1376-1382. doi: 10.1038/ncb1982
129. Sun, Y., Xu, Y., Roy, K., and Price, B. D. (2007). DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity. Mol. Cell. Biol. 27, 8502-8509. doi: 10.1128/MCB.01382-07
130. Sun, Z. W., and Allis, C. D. (2002). Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418, 104-108. doi: 10.1038/nature00883
131. Sy, S. M., Jiang, J., O, W. S., Deng, Y., and Huen, M. S. (2013). The ubiquitin specific protease USP34 promotes ubiquitin signaling at DNA double-strand breaks. Nucleic Acids Res. 41, 8572-8580. doi: 10.1093/nar/gkt622
132. Thorne, A. W., Sautiere, P., Briand, G., and Crane-Robinson, C. (1987). The structure of ubiquitinated histone H2B. EMBO J. 6, 1005-1010.
133. Thorslund, T., Ripplinger, A., Hoffmann, S., Wild, T., Uckelmann, M., Villumsen, B., et al. (2015). Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage. Nature 527, 389-393. doi: 10.1038/nature15401
134. Tuzon, C. T., Spektor, T., Kong, X., Congdon, L. M., Wu, S., Schotta, G., et al. (2014). Concerted activities of distinct H4K20 methyltransferases at DNA double-strand breaks regulate 53BP1 nucleation and NHEJ-directed repair. Cell Rep. 8, 430-438. doi: 10.1016/j.celrep.2014.06.013
135. Typas, D., Luijsterburg, M. S., Wiegant, W. W., Diakatou, M., Helfricht, A., Thijssen, P. E., et al. (2015). The de-ubiquitylating enzymes USP26 and USP37 regulate homologous recombination by counteracting RAP80. Nucleic Acids Res. 43, 6919-6933. doi: 10.1093/nar/gkv613
136. Ui, A., Nagaura, Y., and Yasui, A. (2015). Transcriptional elongation factor ENL phosphorylated by ATM recruits polycomb and switches offtranscription for DSB repair. Mol. Cell 58, 468-482. doi: 10.1016/j.molcel.2015.03.023
137. Wang, B., Matsuoka, S., Ballif, B. A., Zhang, D., Smogorzewska, A., Gygi, S. P., et al. (2007). Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 316, 1194-1198. doi: 10.1126/science.1139476
138. Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R. S., et al. (2004). Role of histone H2A ubiquitination in Polycomb silencing. Nature 431, 873-878. doi: 10.1038/nature02985
139. Wang, J., Aroumougame, A., Lobrich, M., Li, Y., Chen, D., Chen, J., et al. (2014). PTIP associates with Artemis to dictate DNA repair pathway choice. Genes Dev. 28, 2693-2698. doi: 10.1101/gad.252478.114
140. Wiener, R., Zhang, X., Wang, T., and Wolberger, C. (2012). The mechanism of OTUB1-mediated inhibition of ubiquitination. Nature 483, 618-622. doi: 10.1038/nature10911
141. Wiltshire, T. D., Lovejoy, C. A., Wang, T., Xia, F., O'connor, M. J., and Cortez, D. (2010). Sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition identifies ubiquitin-specific peptidase 11 (USP11) as a regulator of DNA double-strand break repair. J. Biol. Chem. 285, 14565-14571. doi: 10.1074/jbc. M110.104745
142. Wood, A., Krogan, N. J., Dover, J., Schneider, J., Heidt, J., Boateng, M. A., et al. (2003). Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol. Cell 11, 267-274. doi: 10.1016/S1097-2765(02)00802-X
143. Wu, C. Y., Kang, H. Y., Yang, W. L., Wu, J., Jeong, Y. S., Wang, J., et al. (2011). Critical role of monoubiquitination of histone H2AX protein in histone H2AX phosphorylation and DNA damage response. J. Biol. Chem. 286, 30806-30815. doi: 10.1074/jbc. M111.257469
144. Wu, L. C., Wang, Z. W., Tsan, J. T., Spillman, M. A., Phung, A., Xu, X. L., et al. (1996). Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat. Genet. 14, 430-440. doi: 10.1038/ng1296-430
145. Wyman, C., and Kanaar, R. (2006). DNA double-strand break repair: all's well that ends well. Annu. Rev. Genet. 40, 363-383. doi: 10.1146/annurev.genet.40.110405.090451
146. Xu, G., Chapman, J. R., Brandsma, I., Yuan, J., Mistrik, M., Bouwman, P., et al. (2015). REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature 521, 541-544. doi: 10.1038/nature14328
147. Yan, J., Kim, Y. S., Yang, X. P., Li, L. P., Liao, G., Xia, F., et al. (2007). The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair response. Cancer Res. 67, 6647-6656. doi: 10.1158/0008-5472.CAN-07-0924
148. Yan, Q., Dutt, S., Xu, R., Graves, K., Juszczynski, P., Manis, J. P., et al. (2009). BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Mol. Cell 36, 110-120. doi: 10.1016/j.molcel.2009.08.019
149. Yan, Q., Xu, R., Zhu, L., Cheng, X., Wang, Z., Manis, J., et al. (2013). BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8. Mol. Cell. Biol. 33, 845-857. doi: 10.1128/MCB.00990-12
150. Yang, H., Pesavento, J. J., Starnes, T. W., Cryderman, D. E., Wallrath, L. L., Kelleher, N. L., et al. (2008). Preferential dimethylation of histone H4 lysine 20 by Suv4-20. J. Biol. Chem. 283, 12085-12092. doi: 10.1074/jbc. M707974200
151. Zhang, D. D., Lo, S. C., Cross, J. V., Templeton, D. J., and Hannink, M. (2004). Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol. Cell. Biol. 24, 10941-10953. doi: 10.1128/MCB.24.24.10941-10953.2004
152. Zhang, Z., Yang, H., and Wang, H. (2014). The histone H2A deubiquitinase USP16 interacts with HERC2 and fine-tunes cellular response to DNA damage. J. Biol. Chem. 289, 32883-32894. doi: 10.1074/jbc. M114.599605
153. Zhu, B., Zheng, Y., Pham, A. D., Mandal, S. S., Erdjument-Bromage, H., Tempst, P., et al. (2005). Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol. Cell 20, 601-611. doi: 10.1016/j.molcel.2005.09.025
154. Zhu, Q., Pao, G. M., Huynh, A. M., Suh, H., Tonnu, N., Nederlof, P. M., et al. (2011). BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477, 179-184. doi: 10.1038/nature10371
155. Zimmermann, M., Lottersberger, F., Buonomo, S. B., Sfeir, A., and de Lange, T. (2013). 53BP1 regulates DSB repair using Rif1 to control 5' end resection. Science 339, 700-704. doi: 10.1126/science.1231573
156. Zong, D., Callen, E., Pegoraro, G., Lukas, C., Lukas, J., and Nussenzweig, A. (2015). Ectopic expression of RNF168 and 53BP1 increases mutagenic but not physiological non-homologous end joining. Nucleic Acids Res. 43, 4950-4961. doi: 10.1093/nar/gkv336