SERBP1 affects homologous recombination-mediated DNA repair by regulation of CtIP translation during S phase

Title
SERBP1 affects homologous recombination-mediated DNA repair by regulation of CtIP translation during S phase
Authors
안장원김선직나우주백수진김정환민기홍염정훈곽호연정선주이철주김선영최철용
Issue Date
2015-07
Publisher
Nucleic acids research
Citation
VOL 43, NO 13, 6321-6333
Abstract
DNA double-strand breaks (DSBs) are the most severe type of DNA damage and are primarily repaired by non-homologous end joining (NHEJ) and homologous recombination (HR) in the G1 and S/G2 phase, respectively. Although CtBP-interacting protein (CtIP) is crucial in DNA end resection during HR following DSBs, little is known about how CtIP levels increase in an S phase-specific manner. Here, we show that Serpine mRNA binding protein 1 (SERBP1) regulates CtIP expression at the translational level in S phase. In response to camptothecin-mediated DNA DSBs, CHK1 and RPA2 phosphorylation, which are hallmarks of HR activation, was abrogated in SERBP1-depleted cells. We identified CtIP mRNA as a binding target of SERBP1 using RNA immunoprecipitation-coupled RNA sequencing, and confirmed SERBP1 binding to CtIP mRNA in S phase. SERBP1 depletion resulted in reduction of polysome-associated CtIP mRNA and concomitant loss of CtIP expression in S phase. These effects were reversed by reconstituting cells with wild-type SERBP1, but not by SERBP1 Delta RGG, an RNA binding defective mutant, suggesting regulation of CtIP translation by SERBP1 association with CtIP mRNA. These results indicate that SERBP1 affects HR-mediated DNA repair in response to DNA DSBs by regulation of CtIP translation in S phase.
URI
http://pubs.kist.re.kr/handle/201004/50536
ISSN
03051048
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KIST Publication > Article
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