The Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins

Nature Communications

Volumn 7, Issue , 2016, Pages

  Grundy, Gabrielle J ^a   Rulten, Stuart L ^a   Arribas Bosacoma, Raquel ^a   Davidson, Kathryn ^a   Kozik, Zuzanna ^a   Oliver, Antony W ^a   Pearl, Laurence H ^a   Caldecott, Keith W ^a  

^a UNIVERSITY OF SUSSEX   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME; ENZYME ACTIVITY; PEPTIDE; PROTEIN;

CELL NUCLEUS ANTIGEN; DNA BINDING PROTEIN; EXODEOXYRIBONUCLEASE; KU ANTIGEN; PROTEIN BINDING; RECQ HELICASE; WERNER SYNDROME ATP DEPENDENT HELICASE; WRN PROTEIN, HUMAN; XRCC6 PROTEIN, HUMAN;

AMINO ACID SEQUENCE; BIOLOGICAL MODEL; CHEMISTRY; CONSERVED SEQUENCE; DNA DAMAGE; DNA END JOINING REPAIR; DOUBLE STRANDED DNA BREAK; HUMAN; METABOLISM; MOLECULAR GENETICS; PROTEIN MOTIF; PROTEIN TERTIARY STRUCTURE;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; ANTIGENS, NUCLEAR; CONSERVED SEQUENCE; DNA BREAKS, DOUBLE-STRANDED; DNA DAMAGE; DNA END-JOINING REPAIR; DNA-BINDING PROTEINS; EXODEOXYRIBONUCLEASES; HUMANS; KU AUTOANTIGEN; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; RECQ HELICASES; WERNER SYNDROME HELICASE;

EID: 84964331216     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms11242     Document Type: Article

References (41)

1. Cannan, W. J. and Pederson, D. S. Mechanisms and consequences of double-strand DNA break formation in chromatin. J. Cell. Physiol. 231, 3-14 (2016).
2. Soulas-Sprauel, P. et al. V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining. Oncogene 26, 7780-7791 (2007).
3. Bunting, S. F. and Nussenzweig, A. End-joining, translocations and cancer. Nat. Rev. Cancer 13, 443-454 (2013).
4. McKinnon, P. J. and Caldecott, K. W. DNA strand break repair and human genetic disease. Annu. Rev. Genomics Hum. Genet. 8, 37-55 (2007).
5. Woodbine, L., Gennery, A. R. and Jeggo, P. A. The clinical impact of deficiency in DNA non-homologous end-joining. DNA Repair (Amst) 16, 84-96 (2014).
6. Chapman, J. R., Taylor, M. R. G. and Boulton, S. J. Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 47, 497-510 (2012).
7. Mahaney, B. L., Meek, K. and Lees-Miller, S. P. Repair of ionizing radiationinduced DNA double-strand breaks by non-homologous end-joining. Biochem. J. 417, 639-650 (2009).
8. Davis, A. J., Chen, B. P. C. and Chen, D. J. DNA-PK: a dynamic enzyme in a versatile DSB repair pathway. DNA Repair (Amst) 17, 21-29 (2014).
9. Ochi, T. et al. Structural biology of DNA repair: spatial organisation of the multicomponent complexes of nonhomologous end joining. J. Nucleic Acids 2010, pii: 621695 (2010).
10. Grundy, G. J., Moulding, H. A., Caldecott, K. W. and Rulten, S. L. One ring to bring them all-The role of Ku in mammalian non-homologous end joining. DNA Repair (Amst) 17, 30-38 (2014).
11. Grundy, G. J. et al. APLF promotes the assembly and activity of nonhomologous end joining protein complexes. EMBO J. 32, 112-125 (2013).
12. Shirodkar, P., Fenton, A. L., Meng, L. and Koch, C. A. Identification and functional characterization of a Ku-binding motif in Aprataxin polynucleotide kinase/phosphatase-like factor (APLF). J. Biol. Chem. 288, 19604-19613 (2013).
13. Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389-3402 (1997).
14. Cooper, M. P. et al. Ku complex interacts with and stimulates the Werner protein. Genes Dev. 14, 907-912 (2000).
15. Li, B. and Comai, L. Functional interaction between Ku and the werner syndrome protein in DNA end processing. J. Biol. Chem. 275, 28349-28352 (2000).
16. Slavoff, S. A., Heo, J., Budnik, B. A., Hanakahi, L. A. and Saghatelian, A. A human short ORF-encoded peptide that stimulates DNA end joining. J. Biol. Chem. C113, 533968 (2014).
17. Harris, R. et al. The 3D solution structure of the C-terminal region of Ku86 (Ku86CTR). J. Mol. Biol. 335, 573-582 (2004).
18. Rivera-Calzada, A., Spagnolo, L., Pearl, L. H. and Llorca, O. Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. EMBO Rep. 8, 56-62 (2007).
19. Walker, J. R., Corpina, R. A. and Goldberg, J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412, 607-614 (2001).
20. Rossi, M. L., Ghosh, A. K. and Bohr, V. A. Roles of Werner syndrome protein in protection of genome integrity. DNA Repair (Amst) 9, 331-344 (2010).
21. Muftuoglu, M. et al. The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis. Hum. Genet. 124, 369-377 (2008).
22. Perry, J. J. P. et al. WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing. Nat. Struct. Mol. Biol. 13, 414-422 (2006).
23. Chen, L. et al. WRN, the protein deficient in Werner syndrome, plays a critical structural role in optimizing DNA repair. Aging Cell 2, 191-199 (2003).
24. Yannone, S. M. et al. Werner syndrome protein is regulated and phosphorylated by DNA-dependent protein kinase. J. Biol. Chem. 276, 38242-38248 (2001).
25. Oshima, J., Huang, S., Pae, C., Campisi, J. and Schiestl, R. H. Lack of WRN results in extensive deletion at nonhomologous joining ends. Cancer Res. 62, 547-551 (2002).
26. Li, B. and Comai, L. Requirements for the nucleolytic processing of DNA ends by the Werner syndrome protein-Ku70/80 complex. J. Biol. Chem. 276, 9896-9902 (2001).
27. Agarwal, S. et al. Isolation, characterization, and genetic complementation of a cellular mutant resistant to retroviral infection. Proc. Natl Acad. Sci. USA 103, 15933-15938 (2006).
28. Ochi, T. et al. DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science 347, 185-188 (2015).
29. Xing, M. et al. Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway. Nat. Commun. 6, 6233 (2015).
30. Yano, K.-I., Morotomi-Yano, K., Lee, K.-J. and Chen, D. J. Functional significance of the interaction with Ku in DNA double-strand break recognition of XLF. FEBS Lett. 585, 841-846 (2011).
31. Andres, S. N. et al. A human XRCC4-XLF complex bridges DNA. Nucleic Acids Res. 40, 1868-1878 (2012).
32. Cheng, W.-H. et al. Linkage between Werner syndrome protein and the Mre11 complex via Nbs1. J. Biol. Chem. 279, 21169-21176 (2004).
33. Otterlei, M. et al. Werner syndrome protein participates in a complex with RAD51, RAD54, RAD54B and ATR in response to ICL-induced replication arrest. J. Cell Sci. 119, 5137-5146 (2006).
34. Trego, K. S. et al. The DNA repair endonuclease XPG interacts directly and functionally with the WRN helicase defective in Werner syndrome. Cell Cycle 10, 1998-2007 (2011).
35. Karmakar, P., Snowden, C. M., Ramsden, D. A. and Bohr, V. A. Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus. Nucleic Acids Res. 30, 3583-3591 (2002).
36. Orren, D. K. et al. A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA. Nucleic Acids Res. 29, 1926-1934 (2001).
37. Fukuchi, K., Martin, G. M. and Monnat, R. J. Mutator phenotype of Werner syndrome is characterized by extensive deletions. Proc. Natl Acad. Sci. USA 86, 5893-5897 (1989).
38. Wyllie, F. S. et al. Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts. Nat. Genet. 24, 16-17 (2000).
39. Kobbe, von C. et al. Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins. J. Biol. Chem. 277, 22035-22044 (2002).
40. Loser, D. A. et al. Sensitization to radiation and alkylating agents by inhibitors of poly(ADP-ribose) polymerase is enhanced in cells deficient in DNA doublestrand break repair. Mol. Cancer Ther. 9, 1775-1787 (2010).
41. Rulten, S. L. et al. PARP-3 and APLF function together to accelerate nonhomologous end-joining. Mol. Cell 41, 33-45 (2011).