title: SERBP1 affects homologous recombination-mediated DNA repair by regulation of CtIP translation during S phase.
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 ΔRGG, 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.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jang-Won
authors.initials: JW
authors.lastname: Ahn
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Sunjik
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Wooju
authors.initials: W
authors.lastname: Na
authors.affiliation: Human Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea Department of Functional Genomics, University of Science of Technology, Daejeon 305-350, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Baek
authors.affiliation: Human Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Keehong
authors.initials: K
authors.lastname: Min
authors.affiliation: Center for Theragnosis, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea Department of Biological Chemistry, University of Science and Technology, Daejeon 305-333, Republic of Korea.
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Yeom
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin 448-701, Republic of Korea.
authors.forename: Hoyun
authors.initials: H
authors.lastname: Kwak
authors.affiliation: Department of Molecular Biology, Dankook University, Yongin 448-701, Republic of Korea.
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Jeong
authors.affiliation: Center for Theragnosis, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea Department of Biological Chemistry, University of Science and Technology, Daejeon 305-333, Republic of Korea.
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
authors.affiliation: Human Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea Department of Functional Genomics, University of Science of Technology, Daejeon 305-350, Republic of Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea choicy@skku.ac.kr.
authors.forename: Cheol Yong
authors.initials: CY
authors.lastname: Choi
mesh_terms: D020413:3' Untranslated Regions; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004706:Endodeoxyribonucleases; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D059767:Recombinational DNA Repair; D016196:S Phase / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C428129:SERBP1 protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human