JWA regulates XRCC1 and functions as a novel base excision repair protein in oxidative-stress-induced DNA single-strand breaks

Shouyu Wang, Zhenghua Gong, Rui Chen, Yunru Liu, Aiping Li, Gang Li, Jianwei Zhou

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

JWA was recently demonstrated to be involved in cellular responses to environmental stress including oxidative stress. Although it was found that JWA protected cells from reactive oxygen species-induced DNA damage, upregulated base excision repair (BER) protein XRCC1 and downregulated PARP-1, the molecular mechanism of JWA in regulating the repair of DNA single-strand breaks (SSBs) is still unclear. Our present studies demonstrated that a reduction in JWA protein levels in cells resulted in a decrease of SSB repair capacity and hypersensitivity to DNA-damaging agents such as methyl methanesulfonate and hydrogen peroxide. JWA functioned as a repair protein by multi-interaction with XRCC1. On the one hand, JWA was translocated into the nucleus by the carrier protein XRCC1 and co-localized with XRCC1 foci after oxidative DNA damage. On the other hand, JWA via MAPK signaling pathway regulated nuclear factor E2F1, which further transcriptionally regulated XRCC1. In addition, JWA protected XRCC1 protein from ubiquitination and degradation by proteasome. These findings indicate that JWA may serve as a novel regulator of XRCC1 in the BER protein complex to facilitate the repair of DNA SSBs.

Original languageEnglish
Pages (from-to)1936-1950
Number of pages15
JournalNucleic Acids Research
Volume37
Issue number6
DOIs
Publication statusPublished - Apr 21 2009
Externally publishedYes

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Single-Stranded DNA Breaks
DNA Repair
Oxidative Stress
DNA Damage
Proteins
Methyl Methanesulfonate
Ubiquitination
Proteasome Endopeptidase Complex
Hydrogen Peroxide
Proteolysis
Reactive Oxygen Species
Carrier Proteins
Hypersensitivity
Down-Regulation
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

JWA regulates XRCC1 and functions as a novel base excision repair protein in oxidative-stress-induced DNA single-strand breaks. / Wang, Shouyu; Gong, Zhenghua; Chen, Rui; Liu, Yunru; Li, Aiping; Li, Gang; Zhou, Jianwei.

In: Nucleic Acids Research, Vol. 37, No. 6, 21.04.2009, p. 1936-1950.

Research output: Contribution to journalArticle

Wang, Shouyu ; Gong, Zhenghua ; Chen, Rui ; Liu, Yunru ; Li, Aiping ; Li, Gang ; Zhou, Jianwei. / JWA regulates XRCC1 and functions as a novel base excision repair protein in oxidative-stress-induced DNA single-strand breaks. In: Nucleic Acids Research. 2009 ; Vol. 37, No. 6. pp. 1936-1950.
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