title: CDK-mediated RNF4 phosphorylation regulates homologous recombination in S-phase.
abstract: There are the two major pathways responsible for the repair of DNA double-strand breaks (DSBs): non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ operates throughout the cell-cycle, while HR is primarily active in the S/G2 phases suggesting that there are cell cycle-specific mechanisms that regulate the balance between NHEJ and HR. Here we reported that CDK2 could phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is important for MDC1 degradation and proper HR repair during S phase. Mutation of the RNF4 phosphorylation sites results in MDC1 stabilization, which in turn compromised HR during S-phase. These results suggest that in addition to drive cell cycle progression, CDK also targets RNF4, which is involved in the regulatory network of DSBs repair.
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China amethystian@hotmail.com.
authors.forename: Kuntian
authors.initials: K
authors.lastname: Luo
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China.
authors.forename: Chenming
authors.initials: C
authors.lastname: Wu
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China yuanjian229@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Division of Oncology Research, Department of Oncology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905, USA lou.zhenkun@mayo.edu.
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Lou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D059767:Recombinational DNA Repair; D016196:S Phase / Q000235:genetics*; D058207:Sumoylation; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; C114070:RNF4 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051357:Cyclin-Dependent Kinase 2