A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination

Nature Structural and Molecular Biology

Volumn 17, Issue 3, 2010, Pages 365-372

  Lee, Dong Hyun ^a   Pan, Yunfeng ^a   Kanner, Shlomo ^b,c   Sung, Patrick ^d   Borowiec, James A ^b,c   Chowdhury, Dipanjan ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b Department of Biochemistry ^*  (Australia)

^c NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHOPROTEIN PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE 4; RAD51 PROTEIN; REPLICATION FACTOR A; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DNA DAMAGE; DNA REPAIR; DOUBLE STRANDED DNA BREAK; ENZYME ACTIVE SITE; HELA CELL; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; HYPERSENSITIVITY; IN VITRO STUDY; KINETICS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; SEQUENCE HOMOLOGY;

ANIMALS; CATALYTIC DOMAIN; CELL CYCLE; CELL LINE; CELL LINE, TUMOR; CELL SURVIVAL; COMET ASSAY; DNA REPAIR; FLUORESCENT ANTIBODY TECHNIQUE; HELA CELLS; HUMANS; IMMUNOPRECIPITATION; KINETICS; PHOSPHOPROTEIN PHOSPHATASES; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN SUBUNITS; RAD51 RECOMBINASE; RECOMBINATION, GENETIC; REPLICATION PROTEIN A; RNA, SMALL INTERFERING; SPODOPTERA;

EID: 77949267720     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.1769     Document Type: Article

References (46)

1. Matsuoka, S. et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160-1166 (2007).
2. Chowdhury, D. et al. γ-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol. Cell 20, 801-809 (2005).
3. Chowdhury, D. et al. A PP4-phosphatase complex dephosphorylates γ-H2AX generated during DNA replication. Mol. Cell 31, 33-46 (2008).
4. Keogh, M.C. et al. A phosphatase complex that dephosphorylates γ-H2AX regulates DNA damage checkpoint recovery. Nature 439, 497-501 (2006).
5. Honkanen, R.E. & Golden, T. Regulators of serine/threonine protein phosphatases at the dawn of a clinical era? Curr. Med. Chem. 9, 2055-2075 (2002).
6. Virshup, D.M. & Shenolikar, S. From promiscuity to precision: protein phosphatases get a makeover. Mol. Cell 33, 537-545 (2009).
7. Janssens, V., Goris, J. & Van Hoof, C. PP2A: the expected tumor suppressor. Curr. Opin. Genet. Dev. 15, 34-41 (2005).
8. Janssens, V., Longin, S. & Goris, J. PP2A holoenzyme assembly: in cauda venenum (the sting is in the tail). Trends Biochem. Sci. 33, 113-121 (2008).
9. Hastie, C.J., Carnegie, G.K., Morrice, N. & Cohen, P.T. A novel 50 kDa protein forms complexes with protein phosphatase 4 and is located at centrosomal microtubule organizing centres. Biochem. J. 347, 845-855 (2000).
10. Nakada, S., Chen, G.I., Gingras, A.C. & Durocher, D. PP4 is a γ-H2AX phosphatase required for recovery from the DNA damage checkpoint. EMBO Rep. 9, 1019-1026 (2008).
11. Anantha, R.W. & Borowiec, J.A. Mitotic crisis: the unmasking of a novel role for RPA. Cell Cycle 8, 357-361 (2009).
12. Fanning, E., Klimovich, V. & Nager, A.R. A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res. 34, 4126-4137 (2006).
13. Zou, Y., Liu, Y., Wu, X. & Shell, S.M. Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses. J. Cell. Physiol. 208, 267-273 (2006).
14. Binz, S.K., Sheehan, A.M. & Wold, M.S. Replication protein A phosphorylation and the cellular response to DNA damage. DNA Repair (Amst.) 3, 1015-1024 (2004).
15. Iftode, C., Daniely, Y. & Borowiec, J.A. Replication protein A (RPA): the eukaryotic SSB. Crit. Rev. Biochem. Mol. Biol. 34, 141-180 (1999).
16. Anantha, R.W., Vassin, V.M. & Borowiec, J.A. Sequential and synergistic modifcation of human RPA stimulates chromosomal DNA repair. J. Biol. Chem. 282, 35910-35923 (2007).
17. Wang, H. et al. Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase. Cancer Res. 61, 8554-8563 (2001).
18. Lu, X., Nannenga, B. & Donehower, L.A. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 19, 1162-1174 (2005).
19. Xia, Y., Ongusaha, P., Lee, S.W. & Liou, Y.C. Loss of Wip1 sensitizes cells to stress-and DNA damage-induced apoptosis. J. Biol. Chem. 284, 17428-17437 (2009).
20. Gingras, A.C. et al. A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity. Mol. Cell. Proteomics 4, 1725-1740 (2005).
21. Xu, Y., Chen, Y., Zhang, P., Jeffrey, P.D. & Shi, Y. Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated τ dephosphorylation. Mol. Cell 31, 873-885 (2008).
22. Sakasai, R. et al. Differential involvement of phosphatidylinositol 3-kinase-related protein kinases in hyperphosphorylation of replication protein A2 in response to replication-mediated DNA double-strand breaks. Genes Cells 11, 237-246 (2006).
23. Cruet-Hennequart, S., Glynn, M.T., Murillo, L.S., Coyne, S. & Carty, M.P. Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-defcient human cells treated with cisplatin and oxaliplatin. DNA Repair (Amst.) 7, 582-596 (2008).
24. Vassin, V.M., Wold, M.S. & Borowiec, J.A. Replication protein A (RPA) phosphorylation prevents RPA association with replication centers. Mol. Cell. Biol. 24, 1930-1943 (2004).
25. Olson, E., Nievera, C.J., Klimovich, V., Fanning, E. & Wu, X. RPA2 is a direct downstream target for ATR to regulate the S-phase checkpoint. J. Biol. Chem. 281, 39517-39533 (2006).
26. Oakley, G.G. et al. RPA phosphorylation in mitosis alters DNA binding and protein-protein interactions. Biochemistry 42, 3255-3264 (2003).
27. Patrick, S.M., Oakley, G.G., Dixon, K. & Turchi, J.J. DNA damage induced hyperphosphorylation of replication protein A. 2. Characterization of DNA binding activity, protein interactions, and activity in DNA replication and repair. Biochemistry 44, 8438-8448 (2005). (Pubitemid 40799924)
28. Zernik-Kobak, M., Vasunia, K., Connelly, M., Anderson, C.W. & Dixon, K. Sites of UV-induced phosphorylation of the p34 subunit of replication protein A from HeLa cells. J. Biol. Chem. 272, 23896-23904 (1997). (Pubitemid 27410971)
29. Shao, R.G. et al. Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA: DNA-PK complexes. EMBO J. 18, 1397-1406 (1999).
30. Anantha, R.W., Sokolova, E. & Borowiec, J.A. RPA phosphorylation facilitates mitotic exit in response to mitotic DNA damage. Proc. Natl. Acad. Sci. USA 105, 12903-12908 (2008).
31. Kim, S.H., Holway, A.H., Wolff, S., Dillin, A. & Michael, W.M. SMK-1/PPH-4.1-mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos. J. Cell Biol. 179, 41-52 (2007).
32. Cimprich, K.A. & Cortez, D. ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 9, 616-627 (2008).
33. San Filippo, J., Sung, P. & Klein, H. Mechanism of eukaryotic homologous recombination. Annu. Rev. Biochem. 77, 229-257 (2008).
34. Weinstock, D.M., Nakanishi, K., Helgadottir, H.R. & Jasin, M. Assaying double-strand break repair pathway choice in mammalian cells using a targeted endonuclease or the RAG recombinase. Methods Enzymol. 409, 524-540 (2006).
35. Sleeth, K.M. et al. RPA mediates recombination repair during replication stress and is displaced from DNA by checkpoint signalling in human cells. J. Mol. Biol. 373, 38-47 (2007).
36. Wang, X. & Haber, J.E. Role of Saccharomyces single-stranded DNA-binding protein RPA in the strand invasion step of double-strand break repair. PLoS Biol. 2, E21 (2004).
37. Sugiyama, T., Zaitseva, E.M. & Kowalczykowski, S.C. A single-stranded DNA-binding protein is needed for effcient presynaptic complex formation by the Saccharomyces cerevisiae Rad51 protein. J. Biol. Chem. 272, 7940-7945 (1997).
38. Wu, X., Yang, Z., Liu, Y. & Zou, Y. Preferential localization of hyperphosphorylated replication protein A to double-strand break repair and checkpoint complexes upon DNA damage. Biochem. J. 391, 473-480 (2005).
39. Douglas, P., Moorhead, G.B., Ye, R. & Lees-Miller, S.P. Protein phosphatases regulate DNA-dependent protein kinase activity. J. Biol. Chem. 276, 18992-18998 (2001).
40. Feng, J. et al. PP2A-dependent dephosphorylation of replication protein A (RPA) is required for the repair of DNA breaks induced by replication stress. Mol. Cell. Biol. 29, 5696-5709 (2009).
41. Speit, G. & Schutz, P. The effect of inhibited replication on DNA migration in the comet assay in relation to cytotoxicity and clastogenicity. Mutat. Res. 655, 22-27 (2008).
42. Petersen, P. et al. Protein phosphatase 2A antagonizes ATM and ATR in a Cdk2-and Cdc7-independent DNA damage checkpoint. Mol. Cell. Biol. 26, 1997-2011 (2006).
43. Chen, G.I. et al. PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4. J. Biol. Chem. 283, 29273-29284 (2008).
44. Pandey, A.V., Mellon, S.H. & Miller, W.L. Protein phosphatase 2A and phosphoprotein SET regulate androgen production by P450c17. J. Biol. Chem. 278, 2837-2844 (2003).
45. Xu, X. & Stern, D.F. NFBD1/KIAA0170 is a chromatin-associated protein involved in DNA damage signaling pathways. J. Biol. Chem. 278, 8795-8803 (2003).
46. Lal, A. et al. miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nat. Struct. Mol. Biol. 16, 492-498 (2009).