Regulatory Functions of Ubiquitin and SUMO in DNA Repair Pathways

  • Stefan Jentsch
  • Stefan Müller
Part of the Subcellular Biochemistry book series (SCBI, volume 54)


Ubiquitin and SUMO are structurally related protein modifiers that are covalently attached to lysine residues of target proteins. While ubiquitin is traditionally known as a signal for proteasomal degradation, its nondegradative actions are equally important in the control of cellular key processes. Similarly, the SUMO system primarily acts in a nondegradative manner. Accumulating evidence indicates that these nonproteolytic functions of ubiquitin and SUMO are particularly important in the control of the DNA damage response network, which coordinates a set of DNA repair pathways and allows cells to cope with different types of genotoxic stress. In this chapter we will illustrate some key functions of ubiquitin and SUMO in the control of selected DNA repair pathways.


Saccharomyces Cerevisiae Regulatory Function Lysine Residue Damage Response Proteasomal Degradation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Seet BT, Dikic I, Zhou MM et al. Reading protein modifications with interaction domains. Nat Rev Mol Cell Biol 2006; 7:473–483.PubMedCrossRefGoogle Scholar
  2. 2.
    Kerscher O, Felberbaum R, Hochstrasser M. Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu Rev Cell Dev Biol 2006; 22:159–180.PubMedCrossRefGoogle Scholar
  3. 3.
    Geoffroy MC, Hay RT. An additional role for SUMO in ubiquitin-mediated proteolysis. Nat Rev Mol Cell Biol 2009; 10:564–568.PubMedCrossRefGoogle Scholar
  4. 4.
    Ulrich HD. The fast-growing business of SUMO chains. Mol Cell 2008; 32:301–305.PubMedCrossRefGoogle Scholar
  5. 5.
    Dikic I, Wakatsuki S, Walters KJ. Ubiquitin-binding domains-from structures to functions. Nat Rev Mol Cell Biol 2009; 10:659–671.PubMedCrossRefGoogle Scholar
  6. 6.
    Kirkin V, Dikic I. Role of ubiquitin-and Ubl-binding proteins in cell signaling. Curr Opin Cell Biol 2007; 19:199–205.PubMedCrossRefGoogle Scholar
  7. 7.
    Bergink S, Jentsch S. Principles of ubiquitin and SUMO modifications in DNA repair. Nature 2009; 458:461–467.PubMedCrossRefGoogle Scholar
  8. 8.
    Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature 2001; 411:366–374.PubMedCrossRefGoogle Scholar
  9. 9.
    Moldovan GL, Pfander B, Jentsch S. PCNA, the maestro of the replication fork. Cell 2007; 129:665–679.PubMedCrossRefGoogle Scholar
  10. 10.
    Hoege C, Pfander B, Moldovan GL et al. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 2002; 419:135–141.PubMedCrossRefGoogle Scholar
  11. 11.
    Bienko M, Green CM, Crosetto N et al. Ubiquitin-binding domains in y-family polymerases regulate translesion synthesis. Science 2005; 310:1821–1824.PubMedCrossRefGoogle Scholar
  12. 12.
    Papouli E, Chen S, Davies AA et al. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol Cell 2005; 19:123–133.PubMedCrossRefGoogle Scholar
  13. 13.
    Pfander B, Moldovan GL, Sacher M et al. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature. 2005; 436:428–433.PubMedGoogle Scholar
  14. 14.
    Moldovan GL, Pfander B, Jentsch S. PCNA controls establishment of sister chromatid cohesion during S phase. Mol Cell 2006; 23:723–732.PubMedCrossRefGoogle Scholar
  15. 15.
    Steinacher R, Schar P. Functionality of human thymine DNA glycosylase requires SUMO-regulated changes in protein conformation. Curr Biol 2005; 15:616–623.PubMedCrossRefGoogle Scholar
  16. 16.
    Baba D, Maita N, Jee JG et al. Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 2005; 435:979–982.PubMedCrossRefGoogle Scholar
  17. 17.
    van Attikum H, Gasser SM. Crosstalk between histone modifications during the DNA damage response. Trends Cell Biol 2009; 19:207–217.PubMedCrossRefGoogle Scholar
  18. 18.
    Moldovan GL, D’Andrea AD. How the Fanconi Anemia Pathway Guards the Genome. Annu Rev Genet 2009.Google Scholar
  19. 19.
    Cohn MA, D’Andrea AD. Chromatin recruitment of DNA repair proteins: lessons from the fanconi anemia and double-strand break repair pathways. Mol Cell 2008; 32:306–312.PubMedCrossRefGoogle Scholar
  20. 20.
    Eckert-Boulet N, Lisby M. Regulation of rDNA stability by sumoylation. DNA Repair (Amst) 2009; 8:507–516.CrossRefGoogle Scholar
  21. 21.
    Sacher M, Pfander B, Hoege C et al. Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat Cell Biol 2006; 8:1284–1290.PubMedCrossRefGoogle Scholar
  22. 22.
    Torres-Rosell J, Sunjevaric I, De Piccoli G et al. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol 2007; 9:923–931.PubMedCrossRefGoogle Scholar
  23. 23.
    Reddel RR. A SUMO ligase for ALT. Nat Struct Mol Biol 2007; 14:570–571.PubMedCrossRefGoogle Scholar
  24. 24.
    Potts PR, Yu H. The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nat Struct Mol Biol 2007; 14:581–590.PubMedCrossRefGoogle Scholar
  25. 25.
    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 2005; 102:4777–4782.PubMedCrossRefGoogle Scholar
  26. 26.
    Kalocsay M, Hiller NJ, Jentsch S. Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol Cell 2009; 33:335–343.PubMedCrossRefGoogle Scholar
  27. 27.
    Oza P, Jaspersen SL, Miele A et al. Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev 2009; 23:912–927.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Department of Molecular Cell BiologyMax Planck Institute of BiochemistryMartinsriedGermany

Personalised recommendations