title: Ubiquitylation of Rad51d Mediated by E3 Ligase Rnf138 Promotes the Homologous Recombination Repair Pathway.
abstract: Ubiquitylation has an important role as a signal transducer that regulates protein function, subcellular localization, or stability during the DNA damage response. In this study, we show that Ring domain E3 ubiquitin ligases RNF138 is recruited to DNA damage site quickly. And the recruitment is mediated through its Zinc finger domains. We further confirm that RNF138 is phosphorylated by ATM at Ser124. However, the phosphorylation was dispensable for recruitment to the DNA damage site. Our findings also indicate that RAD51 assembly at DSB sites following irradiation is dramatically affected in RNF138-deficient cells. Hence, RNF138 is likely involved in regulating homologous recombination repair pathway. Consistently, efficiency of homologous recombination decreased observably in RNF138-depleted cells. In addition, RNF138-deficient cell is hypersensitive to DNA damage insults, such as IR and MMS. And the comet assay confirmed that RNF138 directly participated in DNA damage repair. Moreover, we find that RAD51D directly interacted with RNF138. And the recruitment of RAD51D to DNA damage site is delayed and unstable in RNF138-depleted cells. Taken together, these results suggest that RNF138 promotes the homologous recombination repair pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.|Department of Cancer Genetics and Epigenetics; Beckman Research Institute; City of Hope, Duarte, California, United States of America.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Longchang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Miao
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.|Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Lin-Yu
authors.initials: LY
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Wang
mesh_terms: D002843:Chromatin / Q000737:chemistry; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D059765:Homologous Recombination; D006801:Humans; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic; D059767:Recombinational DNA Repair; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers
chemical_list: D002843:Chromatin; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C577594:RNF138 protein, human; D044767:Ubiquitin-Protein Ligases; D051135:Rad51 Recombinase; D015032:Zinc