HERC2-USP20 Axis Regulates DNA Damage Checkpoint Through Claspin

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2014 Oct 31

PMID 25355518

Citations 40

Authors

Jian Yuan

Kuntian Luo

Min Deng

Yunhui Li

Ping Yin

Bowen Gao

Yuan Fang

Puqiang Wu

Tongzheng Liu

Zhenkun Lou

Affiliations

Soon will be listed here.

Abstract

The DNA damage response triggers cell-cycle checkpoints, DNA repair and apoptosis using multiple post-translational modifications as molecular switches. However, how ubiquitination regulates ATR signaling in response to replication stress and single-strand break is still unclear. Here, we identified the deubiquitination enzyme (DUB) USP20 as a pivotal regulator of ATR-related DDR pathway. Through screening a panel of DUBs, we identified USP20 as critical for replication stress response. USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization. USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling. These findings reveal USP20 to be a novel regulator of ATR-dependent DNA damage signaling.

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References

Rendtlew Danielsen J, Povlsen L, Villumsen B, Streicher W, Nilsson J, Wikstrom M . DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. J Cell Biol. 2012; 197(2):179-87. PMC: 3328386. DOI: 10.1083/jcb.201106152. View

Flynn R, Zou L . ATR: a master conductor of cellular responses to DNA replication stress. Trends Biochem Sci. 2010; 36(3):133-40. PMC: 3024454. DOI: 10.1016/j.tibs.2010.09.005. View

Kastan M, Bartek J . Cell-cycle checkpoints and cancer. Nature. 2004; 432(7015):316-23. DOI: 10.1038/nature03097. View

Zou L, Elledge S . Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science. 2003; 300(5625):1542-8. DOI: 10.1126/science.1083430. View

Jackson S, Bartek J . The DNA-damage response in human biology and disease. Nature. 2009; 461(7267):1071-8. PMC: 2906700. DOI: 10.1038/nature08467. View

Costanzo V, Shechter D, Lupardus P, Cimprich K, Gottesman M, Gautier J . An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Mol Cell. 2003; 11(1):203-13. DOI: 10.1016/s1097-2765(02)00799-2. View

Wang X, Zou L, Lu T, Bao S, Hurov K, Hittelman W . Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol Cell. 2006; 23(3):331-41. DOI: 10.1016/j.molcel.2006.06.022. View

Delacroix S, Wagner J, Kobayashi M, Yamamoto K, Karnitz L . The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev. 2007; 21(12):1472-7. PMC: 1891424. DOI: 10.1101/gad.1547007. View

Ciccia A, Elledge S . The DNA damage response: making it safe to play with knives. Mol Cell. 2010; 40(2):179-204. PMC: 2988877. DOI: 10.1016/j.molcel.2010.09.019. View

10.

Cortez D, Guntuku S, Qin J, Elledge S . ATR and ATRIP: partners in checkpoint signaling. Science. 2001; 294(5547):1713-6. DOI: 10.1126/science.1065521. View

11.

Liu S, Shiotani B, Lahiri M, Marechal A, Tse A, Leung C . ATR autophosphorylation as a molecular switch for checkpoint activation. Mol Cell. 2011; 43(2):192-202. PMC: 3155885. DOI: 10.1016/j.molcel.2011.06.019. View

12.

Stokes M, Rush J, MacNeill J, Min Ren J, Sprott K, Nardone J . Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci U S A. 2007; 104(50):19855-60. PMC: 2148387. DOI: 10.1073/pnas.0707579104. View

13.

Matsuoka S, Ballif B, Smogorzewska A, McDonald 3rd E, Hurov K, Luo J . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6. DOI: 10.1126/science.1140321. View

14.

Shanmugam I, Abbas M, Ayoub F, Mirabal S, Bsaili M, Caulder E . Ubiquitin-specific peptidase 20 regulates Rad17 stability, checkpoint kinase 1 phosphorylation and DNA repair by homologous recombination. J Biol Chem. 2014; 289(33):22739-22748. PMC: 4132780. DOI: 10.1074/jbc.M114.550459. View

15.

Bao S, Lu T, Wang X, Zheng H, Wang L, Wei Q . Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects. Oncogene. 2004; 23(33):5586-93. DOI: 10.1038/sj.onc.1207753. View

16.

Wang J, Gong Z, Chen J . MDC1 collaborates with TopBP1 in DNA replication checkpoint control. J Cell Biol. 2011; 193(2):267-73. PMC: 3080258. DOI: 10.1083/jcb.201010026. View

17.

Curcio-Morelli C, Zavacki A, Christofollete M, Gereben B, de Freitas B, Harney J . Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. J Clin Invest. 2003; 112(2):189-96. PMC: 164294. DOI: 10.1172/JCI18348. View

18.

Mailand N, Bekker-Jensen S, Bartek J, Lukas J . Destruction of Claspin by SCFbetaTrCP restrains Chk1 activation and facilitates recovery from genotoxic stress. Mol Cell. 2006; 23(3):307-18. DOI: 10.1016/j.molcel.2006.06.016. View

19.

Bekker-Jensen S, Rendtlew Danielsen J, Fugger K, Gromova I, Nerstedt A, Lukas C . HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat Cell Biol. 2009; 12(1):80-6. DOI: 10.1038/ncb2008. View

20.

Yasunaga J, Lin F, Lu X, Jeang K . Ubiquitin-specific peptidase 20 targets TRAF6 and human T cell leukemia virus type 1 tax to negatively regulate NF-kappaB signaling. J Virol. 2011; 85(13):6212-9. PMC: 3126525. DOI: 10.1128/JVI.00079-11. View