PIAS3 promotes homology‑directed repair and distal non‑homologous end joining

Liu,Shicui; Fan,Zhongyi; Geng,Zhengying; Zhang,Hao; Ye,Qinong; Jiao,Shunchang; Xu,Xiaojie

doi:10.3892/ol.2013.1472

PIAS3 promotes homology‑directed repair and distal non‑homologous end joining

Authors:
- Shicui Liu
- Zhongyi Fan
- Zhengying Geng
- Hao Zhang
- Qinong Ye
- Shunchang Jiao
- Xiaojie Xu
View Affiliations

Affiliations: School of Medicine, Nankai University, Tianjin 300071, P.R. China, Department of Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, P.R. China
Published online on: July 17, 2013 https://doi.org/10.3892/ol.2013.1472
Pages: 1045-1048

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

A DNA double‑strand break (DSB) is the most severe form of DNA damage and is mainly repaired through homologous recombination (HR), which has a high fidelity, or non‑homologous end joining (NHEJ), which is prone to errors. Defects in the DNA damage response lead to genomic instability and ultimately the predisposition of organs to cancer. Protein inhibitor of activated STAT‑1 (PIAS1), which is a potential small ubiquitin‑related modifier (SUMO) ligase, has been reported to be involved in DSB repair. The present study identified that another member of the PIAS family, PIAS3, is also an enhancer for HR‑ and NHEJ‑mediated DSB repair. Furthermore, the overexpression of PIAS3 was demonstrated to increase the resistance of HeLa cells to ionizing radiation (IR), indicating a significant role for PIAS3 in the DNA damage response (DDR) pathway.

View Figures

View References

1	Yang J, Yu Y, Hamrick HE and Duerksen-Hughes PJ: ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis. 24:1571–1580. 2003. View Article : Google Scholar : PubMed/NCBI
2	David R: DNA damage response: restricting repair. Nat Rev Mol Cell Biol. 13:6012012. View Article : Google Scholar : PubMed/NCBI
3	Schwartz D and Rotter V: p53-dependent cell cycle control: response to genotoxic stress. Semin Cancer Biol. 8:325–336. 1998. View Article : Google Scholar : PubMed/NCBI
4	Surova O and Zhivotovsky B: Various modes of cell death induced by DNA damage. Oncogene. Dec 3–2012.(Epub ahead of print).
5	Helmink BA and Sleckman BP: The response to and repair of RAG-mediated DNA double-strand breaks. Annu Rev Immunol. 30:175–202. 2012. View Article : Google Scholar : PubMed/NCBI
6	Takata M, Sasaki MS, Sonoda E, et al: Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J. 17:5497–5508. 1998. View Article : Google Scholar
7	Bennardo N, Cheng A, Huang N and Stark JM: Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet. 4:e10001102008. View Article : Google Scholar : PubMed/NCBI
8	Panier S and Durocher D: Regulatory ubiquitylation in response to DNA double-strand breaks. DNA Repair (Amst). 8:436–443. 2009. View Article : Google Scholar : PubMed/NCBI
9	Galanty Y, Belotserkovskaya R, Coates J, Polo S, Miller KM and Jackson SP: Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature. 462:935–939. 2009. View Article : Google Scholar : PubMed/NCBI
10	Galanty Y, Belotserkovskaya R, Coates J and Jackson SP: RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair. Genes Dev. 26:1179–1195. 2012. View Article : Google Scholar : PubMed/NCBI
11	Zhu J, Zhu S, Guzzo CM, et al: Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification. J Biol Chem. 283:29405–29415. 2008. View Article : Google Scholar : PubMed/NCBI
12	Sharrocks AD: PIAS proteins and transcriptional regulation - more than just SUMO E3 ligases. Genes Dev. 20:754–758. 2006. View Article : Google Scholar : PubMed/NCBI
13	Polo SE and Jackson SP: Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 25:409–433. 2011. View Article : Google Scholar : PubMed/NCBI
14	Yan J, Zhu J, Zhong H, Lu Q, Huang C and Ye Q: BRCA1 interacts with FHL2 and enhances FHL2 transactivation function. FEBS Lett. 553:183–189. 2003. View Article : Google Scholar : PubMed/NCBI
15	Bennardo N, Gunn A, Cheng A, Hasty P and Stark JM: Limiting the persistence of a chromosome break diminishes its mutagenic potential. PLoS Genet. 5:e10006832009. View Article : Google Scholar : PubMed/NCBI
16	Laulier C, Cheng A and Stark JM: The relative efficiency of homology-directed repair has distinct effects on proper anaphase chromosome separation. Nucleic Acids Res. 39:5935–5944. 2011. View Article : Google Scholar
17	Yunus AA and Lima CD: Structure of the Siz/PIAS SUMO E3 ligase Siz1 and determinants required for SUMO modification of PCNA. Mol Cell. 35:669–682. 2009. View Article : Google Scholar : PubMed/NCBI
18	Rosas-Acosta G, Langereis MA, Deyrieux A and Wilson VG: Proteins of the PIAS family enhance the sumoylation of the papillomavirus E1 protein. Virology. 331:190–203. 2005. View Article : Google Scholar : PubMed/NCBI
19	Schmidt D and Müller S: Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity. Proc Natl Acad Sci USA. 99:2872–2877. 2002. View Article : Google Scholar : PubMed/NCBI
20	Jackson PK: A new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases. Genes Dev. 15:3053–3058. 2001. View Article : Google Scholar : PubMed/NCBI
21	Duval D, Duval G, Kedinger C, Poch O and Boeuf H: The ‘PINIT’ motif, of a newly identified conserved domain of the PIAS protein family, is essential for nuclear retention of PIAS3L. FEBS Lett. 554:111–118. 2003.
22	Weitzel JN, Clague J, Martir-Negron A, et al: Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network. J Clin Oncol. 31:210–216. 2013. View Article : Google Scholar
23	Gannon HS, Woda BA and Jones SN: ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice. Cancer Cell. 21:668–679. 2012. View Article : Google Scholar : PubMed/NCBI
24	Squatrito M, Brennan CW, Helmy K, Huse JT, Petrini JH and Holland EC: Loss of ATM/Chk2/p53 pathway components accelerates tumor development and contributes to radiation resistance in gliomas. Cancer Cell. 18:619–629. 2010. View Article : Google Scholar : PubMed/NCBI
25	Rodriguez-Wallberg KA and Oktay K: Fertility preservation and pregnancy in women with and without BRCA mutation-positive breast cancer. Oncologist. 17:1409–1417. 2012. View Article : Google Scholar : PubMed/NCBI
26	Hartman AR, Kaldate RR, Sailer LM, et al: Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer. Cancer. 118:2787–2795. 2012. View Article : Google Scholar : PubMed/NCBI