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Two-way communications between ubiquitin-like modifiers and DNA

Nature Structural & Molecular Biology volume 21, pages 317–324 (2014)Cite this article

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Abstract

Many aspects of nucleic acid metabolism, such as DNA replication, repair and transcription, are regulated by the post-translational modifiers ubiquitin and SUMO. Not surprisingly, DNA itself plays an integral part in determining the modification of most chromatin-associated targets. Conversely, ubiquitination or SUMOylation of a protein can impinge on its DNA-binding properties. This review describes mechanistic principles governing the mutual interactions between DNA and ubiquitin or SUMO.

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Figure 1: Direct recruitment of E3 by DNA.
Figure 2: PCNA can act as a substrate or an interaction platform for chromatin-associated modification reactions.
Figure 3: E3 recruitment by DNA-binding proteins.
Figure 4: E3 recruitment by post-translational modifications.

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References

  1. Flotho, A. & Melchior, F. SUMOylation: a regulatory protein modification in health and disease. Annu. Rev. Biochem. 82, 357–385 (2013).

    Article  CAS  PubMed  Google Scholar 

  2. Jackson, S.P. & Durocher, D. Regulation of DNA damage responses by ubiquitin and SUMO. Mol. Cell 49, 795–807 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. Kerscher, O., Felberbaum, R. & Hochstrasser, M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu. Rev. Cell Dev. Biol. 22, 159–180 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. Ulrich, H.D. & Walden, H. Ubiquitin signalling in DNA replication and repair. Nat. Rev. Mol. Cell Biol. 11, 479–489 (2010).

    Article  CAS  PubMed  Google Scholar 

  5. Geng, F., Wenzel, S. & Tansey, W.P. Ubiquitin and proteasomes in transcription. Annu. Rev. Biochem. 81, 177–201 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gill, G. SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev. 18, 2046–2059 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Müller, S., Ledl, A. & Schmidt, D. SUMO: a regulator of gene expression and genome integrity. Oncogene 23, 1998–2008 (2004).

    Article  PubMed  CAS  Google Scholar 

  8. Bergink, S. & Jentsch, S. Principles of ubiquitin and SUMO modifications in DNA repair. Nature 458, 461–467 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Aravind, L. & Koonin, E.V. SAP: a putative DNA-binding motif involved in chromosomal organization. Trends Biochem. Sci. 25, 112–114 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Palvimo, J.J. PIAS proteins as regulators of small ubiquitin-related modifier (SUMO) modifications and transcription. Biochem. Soc. Trans. 35, 1405–1408 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Suzuki, R. et al. Solution structures and DNA binding properties of the N-terminal SAP domains of SUMO E3 ligases from Saccharomyces cerevisiae and Oryza sativa. Proteins 75, 336–347 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Hoege, C., Pfander, B., Moldovan, G.L., Pyrowolakis, G. & Jentsch, S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419, 135–141 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Huttner, D. & Ulrich, H.D. Cooperation of replication protein A with the ubiquitin ligase Rad18 in DNA damage bypass. Cell Cycle 7, 3629–3633 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Nakajima, S. et al. Replication-dependent and -independent responses of RAD18 to DNA damage in human cells. J. Biol. Chem. 281, 34687–34695 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Notenboom, V. et al. Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification. Nucleic Acids Res. 35, 5819–5830 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tsuji, Y. et al. Recognition of forked and single-stranded DNA structures by human RAD18 complexed with RAD6B protein triggers its recruitment to stalled replication forks. Genes Cells 13, 343–354 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Hopfner, K.P., Gerhold, C.B., Lakomek, K. & Wollmann, P. Swi2/Snf2 remodelers: hybrid views on hybrid molecular machines. Curr. Opin. Struct. Biol. 22, 225–233 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Eisen, J.A., Sweder, K.S. & Hanawalt, P.C. Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions. Nucleic Acids Res. 23, 2715–2723 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lawrence, C. The RAD6 DNA repair pathway in Saccharomyces cerevisiae: what does it do, and how does it do it? BioEssays 16, 253–258 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Parker, J.L. & Ulrich, H.D. Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5. EMBO J. 28, 3657–3666 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Garg, P. & Burgers, P.M. Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases η and REV1. Proc. Natl. Acad. Sci. USA 102, 18361–18366 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Iyer, L.M., Babu, M.M. & Aravind, L. The HIRAN domain and recruitment of chromatin remodeling and repair activities to damaged DNA. Cell Cycle 5, 775–782 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Blastyák, A., Hajdu, I., Unk, I. & Haracska, L. Role of double-stranded DNA translocase activity of human HLTF in replication of damaged DNA. Mol. Cell. Biol. 30, 684–693 (2010).

    Article  PubMed  CAS  Google Scholar 

  24. Blastyák, A. et al. Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression. Mol. Cell 28, 167–175 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Sriramachandran, A.M. & Dohmen, R.J. SUMO-targeted ubiquitin ligases. Biochim. Biophys. Acta 1843, 75–85 (2014).

    Article  CAS  PubMed  Google Scholar 

  26. Uzunova, K. et al. Ubiquitin-dependent proteolytic control of SUMO conjugates. J. Biol. Chem. 282, 34167–34175 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Lescasse, R., Pobiega, S., Callebaut, I. & Marcand, S. End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1. EMBO J. 32, 805–815 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Häkli, M., Karvonen, U., Janne, O.A. & Palvimo, J.J. The RING finger protein SNURF is a bifunctional protein possessing DNA binding activity. J. Biol. Chem. 276, 23653–23660 (2001).

    Article  PubMed  Google Scholar 

  29. Vidal, M. Role of polycomb proteins Ring1A and Ring1B in the epigenetic regulation of gene expression. Int. J. Dev. Biol. 53, 355–370 (2009).

    Article  CAS  PubMed  Google Scholar 

  30. Bentley, M.L. et al. Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin ligase complex. EMBO J. 30, 3285–3297 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Scrima, A. et al. Detecting UV-lesions in the genome: the modular CRL4 ubiquitin ligase does it best!. FEBS Lett. 585, 2818–2825 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Sugasawa, K. Regulation of damage recognition in mammalian global genomic nucleotide excision repair. Mutat. Res. 685, 29–37 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Fischer, E.S. et al. The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation. Cell 147, 1024–1039 (2011).

    Article  CAS  PubMed  Google Scholar 

  34. Yeh, J.I. et al. Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) dimerization and its roles in chromatinized DNA repair. Proc. Natl. Acad. Sci. USA 109, E2737–E2746 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kegel, A. & Sjogren, C. The Smc5/6 complex: more than repair? Cold Spring Harb. Symp. Quant. Biol. 75, 179–187 (2010).

    Article  CAS  PubMed  Google Scholar 

  36. Wu, N. & Yu, H. The Smc complexes in DNA damage response. Cell Biosci. 2, 5 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Andrews, E.A. et al. Nse2, a component of the Smc5–6 complex, is a SUMO ligase required for the response to DNA damage. Mol. Cell. Biol. 25, 185–196 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Duan, X. et al. Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Mol. Cell 35, 657–668 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Potts, P.R. & Yu, H. Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol. Cell. Biol. 25, 7021–7032 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhao, X. & Blobel, G. A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc. Natl. Acad. Sci. USA 102, 4777–4782 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Doyle, J.M., Gao, J., Wang, J., Yang, M. & Potts, P.R. MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol. Cell 39, 963–974 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kim, H. & D'Andrea, A.D. Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway. Genes Dev. 26, 1393–1408 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kottemann, M.C. & Smogorzewska, A. Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature 493, 356–363 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Coulthard, R. et al. Architecture and DNA recognition elements of the Fanconi anemia FANCM-FAAP24 complex. Structure 21, 1648–1658 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tao, Y. et al. The structure of the FANCM–MHF complex reveals physical features for functional assembly. Nat. Commun. 3, 782 (2012).

    Article  PubMed  CAS  Google Scholar 

  46. Morohashi, H., Maculins, T. & Labib, K. The amino-terminal TPR domain of Dia2 tethers SCFDia2 to the replisome progression complex. Curr. Biol. 19, 1943–1949 (2009).

    Article  CAS  PubMed  Google Scholar 

  47. Mimura, S., Komata, M., Kishi, T., Shirahige, K. & Kamura, T. SCFDia2 regulates DNA replication forks during S-phase in budding yeast. EMBO J. 28, 3693–3705 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Andress, E.J., Holic, R., Edelmann, M.J., Kessler, B.M. & Yu, V.P. Dia2 controls transcription by mediating assembly of the RSC complex. PLoS ONE 6, e21172 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim, J. & Roeder, R.G. Direct Bre1-Paf1 complex interactions and RING finger-independent Bre1-Rad6 interactions mediate histone H2B ubiquitylation in yeast. J. Biol. Chem. 284, 20582–20592 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Davies, A.A., Huttner, D., Daigaku, Y., Chen, S. & Ulrich, H.D. Activation of ubiquitin-dependent DNA damage bypass is mediated by Replication Protein A. Mol. Cell 29, 625–636 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Niimi, A. et al. Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells. Proc. Natl. Acad. Sci. USA 105, 16125–16130 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Al-Hakim, A. et al. The ubiquitous role of ubiquitin in the DNA damage response. DNA Repair (Amst.) 9, 1229–1240 (2010).

    Article  CAS  Google Scholar 

  53. Bekker-Jensen, S. & Mailand, N. The ubiquitin- and SUMO-dependent signaling response to DNA double-strand breaks. FEBS Lett. 585, 2914–2919 (2011).

    Article  CAS  PubMed  Google Scholar 

  54. Ulrich, H.D. Ubiquitin and SUMO in DNA repair at a glance. J. Cell Sci. 125, 249–254 (2012).

    Article  CAS  PubMed  Google Scholar 

  55. Mermershtain, I. & Glover, J.N. Structural mechanisms underlying signaling in the cellular response to DNA double strand breaks. Mutat. Res. 750, 15–22 (2013).

    Article  CAS  PubMed  Google Scholar 

  56. Lou, Z. et al. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell 21, 187–200 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Stewart, G.S., Wang, B., Bignell, C.R., Taylor, A.M. & Elledge, S.J. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 421, 961–966 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Stucki, M. et al. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123, 1213–1226 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Huen, M.S. et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131, 901–914 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kolas, N.K. et al. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318, 1637–1640 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Mailand, N. et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131, 887–900 (2007).

    Article  CAS  PubMed  Google Scholar 

  62. Bekker-Jensen, S. et al. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat. Cell Biol. 12, 80–86 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Doil, C. et al. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell 136, 435–446 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Stewart, G.S. et al. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell 136, 420–434 (2009).

    Article  CAS  PubMed  Google Scholar 

  65. Mattiroli, F. et al. RNF168 ubiquitinates K13–15 on H2A/H2AX to drive DNA damage signaling. Cell 150, 1182–1195 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Panier, S. et al. Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks. Mol. Cell 47, 383–395 (2012).

    Article  CAS  PubMed  Google Scholar 

  67. Kim, H., Chen, J. & Yu, X. Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316, 1202–1205 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Liu, Z., Wu, J. & Yu, X. CCDC98 targets BRCA1 to DNA damage sites. Nat. Struct. Mol. Biol. 14, 716–720 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. Sobhian, B. et al. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316, 1198–1202 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wang, B. et al. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 316, 1194–1198 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Paull, T.T., Cortez, D., Bowers, B., Elledge, S.J. & Gellert, M. Direct DNA binding by Brca1. Proc. Natl. Acad. Sci. USA 98, 6086–6091 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Yamane, K., Katayama, E. & Tsuruo, T. The BRCT regions of tumor suppressor BRCA1 and of XRCC1 show DNA end binding activity with a multimerizing feature. Biochem. Biophys. Res. Commun. 279, 678–684 (2000).

    Article  CAS  PubMed  Google Scholar 

  73. Huang, J. et al. RAD18 transmits DNA damage signalling to elicit homologous recombination repair. Nat. Cell Biol. 11, 592–603 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Vyas, R. et al. RNF4 is required for DNA double-strand break repair in vivo. Cell Death Differ. 20, 490–502 (2013).

    Article  CAS  PubMed  Google Scholar 

  75. Yin, Y. et al. SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage. Genes Dev. 26, 1196–1208 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Galanty, Y., Belotserkovskaya, R., Coates, J. & Jackson, S.P. RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair. Genes Dev. 26, 1179–1195 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Parker, J.L. & Ulrich, H.D. A SUMO-interacting motif activates budding yeast ubiquitin ligase Rad18 towards SUMO-modified PCNA. Nucleic Acids Res. 40, 11380–11388 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Havens, C.G. & Walter, J.C. Mechanism of CRL4Cdt2, a PCNA-dependent E3 ubiquitin ligase. Genes Dev. 25, 1568–1582 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Arias, E.E. & Walter, J.C. Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. Genes Dev. 19, 114–126 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hu, J., McCall, C.M., Ohta, T. & Xiong, Y. Targeted ubiquitination of CDT1 by the DDB1–CUL4A–ROC1 ligase in response to DNA damage. Nat. Cell Biol. 6, 1003–1009 (2004).

    Article  CAS  PubMed  Google Scholar 

  81. Kondo, T. et al. Rapid degradation of Cdt1 upon UV-induced DNA damage is mediated by SCFSkp2 complex. J. Biol. Chem. 279, 27315–27319 (2004).

    Article  CAS  PubMed  Google Scholar 

  82. Arias, E.E. & Walter, J.C. PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication. Nat. Cell Biol. 8, 84–90 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Hu, J. & Xiong, Y. An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage. J. Biol. Chem. 281, 3753–3756 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Jin, J., Arias, E.E., Chen, J., Harper, J.W. & Walter, J.C. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol. Cell 23, 709–721 (2006).

    Article  CAS  PubMed  Google Scholar 

  85. Senga, T. et al. PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. J. Biol. Chem. 281, 6246–6252 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. Havens, C.G. & Walter, J.C. Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2. Mol. Cell 35, 93–104 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Havens, C.G. et al. Direct role for proliferating cell nuclear antigen in substrate recognition by the E3 ubiquitin ligase CRL4Cdt2. J. Biol. Chem. 287, 11410–11421 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kim, Y., Starostina, N.G. & Kipreos, E.T. The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing. Genes Dev. 22, 2507–2519 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Nishitani, H. et al. CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4–DDB1Cdt2 pathway during S phase and after UV irradiation. J. Biol. Chem. 283, 29045–29052 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Abbas, T. et al. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev. 22, 2496–2506 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Centore, R.C. et al. CRL4Cdt2-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase. Mol. Cell 40, 22–33 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Liu, C. et al. Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms. Genes Dev. 17, 1130–1140 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bacquin, A. et al. The helicase FBH1 is tightly regulated by PCNA via CRL4Cdt2-mediated proteolysis in human cells. Nucleic Acids Res. 41, 6501–6513 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Shibutani, S.T. et al. Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev. Cell 15, 890–900 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kim, S.H. & Michael, W.M. Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans. Mol. Cell 32, 757–766 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Mortensen, U.H., Bendixen, C., Sunjevaric, I. & Rothstein, R. DNA strand annealing is promoted by the yeast Rad52 protein. Proc. Natl. Acad. Sci. USA 93, 10729–10734 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Shinohara, A., Shinohara, M., Ohta, T., Matsuda, S. & Ogawa, T. Rad52 forms ring structures and co-operates with RPA in single-strand DNA annealing. Genes Cells 3, 145–156 (1998).

    Article  CAS  PubMed  Google Scholar 

  98. Sacher, M., Pfander, B., Hoege, C. & Jentsch, S. Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat. Cell Biol. 8, 1284–1290 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. Torres-Rosell, J. et al. The Smc5–Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat. Cell Biol. 9, 923–931 (2007).

    Article  CAS  PubMed  Google Scholar 

  100. Altmannova, V. et al. Rad52 SUMOylation affects the efficiency of the DNA repair. Nucleic Acids Res. 38, 4708–4721 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Papouli, E. et al. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol. Cell 19, 123–133 (2005).

    Article  CAS  PubMed  Google Scholar 

  102. Pfander, B., Moldovan, G.L., Sacher, M., Hoege, C. & Jentsch, S. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature 436, 428–433 (2005).

    Article  CAS  PubMed  Google Scholar 

  103. Parker, J.L. et al. SUMO modification of PCNA is controlled by DNA. EMBO J. 27, 2422–2431 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Windecker, H. & Ulrich, H.D. Architecture and assembly of poly-SUMO chains on PCNA in Saccharomyces cerevisiae. J. Mol. Biol. 376, 221–231 (2008).

    Article  CAS  PubMed  Google Scholar 

  105. Eilebrecht, S., Smet-Nocca, C., Wieruszeski, J.M. & Benecke, A. SUMO-1 possesses DNA binding activity. BMC Res. Notes 3, 146 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Zilio, N. et al. DNA-dependent SUMO modification of PARP-1. DNA Repair (Amst.) 12, 761–773 (2013).

    Article  CAS  Google Scholar 

  107. Woodhouse, B.C. & Dianov, G.L. Poly ADP-ribose polymerase-1: an international molecule of mystery. DNA Repair (Amst.) 7, 1077–1086 (2008).

    Article  CAS  Google Scholar 

  108. Martin, N. et al. PARP-1 transcriptional activity is regulated by SUMOylation upon heat shock. EMBO J. 28, 3534–3548 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Messner, S. et al. SUMOylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function. FASEB J. 23, 3978–3989 (2009).

    Article  CAS  PubMed  Google Scholar 

  110. Wilson, M.D., Harreman, M. & Svejstrup, J.Q. Ubiquitylation and degradation of elongating RNA polymerase II: the last resort. Biochim. Biophys. Acta 1829, 151–157 (2013).

    Article  CAS  PubMed  Google Scholar 

  111. Harreman, M. et al. Distinct ubiquitin ligases act sequentially for RNA polymerase II polyubiquitylation. Proc. Natl. Acad. Sci. USA 106, 20705–20710 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Somesh, B.P. et al. Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases undergoing transcriptional arrest. Cell 121, 913–923 (2005).

    Article  CAS  PubMed  Google Scholar 

  113. Somesh, B.P. et al. Communication between distant sites in RNA polymerase II through ubiquitylation factors and the polymerase CTD. Cell 129, 57–68 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Wilson, M.D. et al. Proteasome-mediated processing of Def1, a critical step in the cellular response to transcription stress. Cell 154, 983–995 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Woudstra, E.C. et al. A Rad26–Def1 complex coordinates repair and RNA pol II proteolysis in response to DNA damage. Nature 415, 929–933 (2002).

    Article  CAS  PubMed  Google Scholar 

  116. Nakagawa, K. & Yokosawa, H. Degradation of transcription factor IRF-1 by the ubiquitin-proteasome pathway: the C-terminal region governs the protein stability. Eur. J. Biochem. 267, 1680–1686 (2000).

    Article  CAS  PubMed  Google Scholar 

  117. Landré, V., Pion, E., Narayan, V., Xirodimas, D.P. & Ball, K.L. DNA-binding regulates site-specific ubiquitination of IRF-1. Biochem. J. 449, 707–717 (2013).

    Article  PubMed  CAS  Google Scholar 

  118. Cortázar, D., Kunz, C., Saito, Y., Steinacher, R. & Schar, P. The enigmatic thymine DNA glycosylase. DNA Repair (Amst.) 6, 489–504 (2007).

    Article  CAS  Google Scholar 

  119. Hardeland, U., Steinacher, R., Jiricny, J. & Schär, P. Modification of the human thymine-DNA glycosylase by ubiquitin-like proteins facilitates enzymatic turnover. EMBO J. 21, 1456–1464 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Fitzgerald, M.E. & Drohat, A.C. Coordinating the initial steps of base excision repair: apurinic/apyrimidinic endonuclease 1 actively stimulates thymine DNA glycosylase by disrupting the product complex. J. Biol. Chem. 283, 32680–32690 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Baba, D. et al. Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 435, 979–982 (2005).

    Article  CAS  PubMed  Google Scholar 

  122. Steinacher, R. & Schar, P. Functionality of human thymine DNA glycosylase requires SUMO-regulated changes in protein conformation. Curr. Biol. 15, 616–623 (2005).

    Article  CAS  PubMed  Google Scholar 

  123. Kapetanaki, M.G. et al. The DDB1–CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. Proc. Natl. Acad. Sci. USA 103, 2588–2593 (2006).

    Article  CAS  PubMed  Google Scholar 

  124. Wang, H. et al. Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol. Cell 22, 383–394 (2006).

    Article  PubMed  CAS  Google Scholar 

  125. Lan, L. et al. Monoubiquitinated histone H2A destabilizes photolesion-containing nucleosomes with concomitant release of UV-damaged DNA-binding protein E3 ligase. J. Biol. Chem. 287, 12036–12049 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Shilatifard, A. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu. Rev. Biochem. 75, 243–269 (2006).

    Article  CAS  PubMed  Google Scholar 

  127. Sato, K., Toda, K., Ishiai, M., Takata, M. & Kurumizaka, H. DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI. Nucleic Acids Res. 40, 4553–4561 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Research in the author's laboratory is supported by the Boehringer Ingelheim Foundation.

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  1. Institute of Molecular Biology, Mainz, Germany

    Helle D Ulrich & Helle D Ulrich

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Ulrich, H. Two-way communications between ubiquitin-like modifiers and DNA. Nat Struct Mol Biol 21, 317–324 (2014). https://doi.org/10.1038/nsmb.2805

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