title: Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) promotes non-homologous end joining and inhibits homologous recombination repair upon DNA damage.
abstract: Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) has been shown to be involved in gene silencing and DNA damage. However, the exact mechanisms of how SMCHD1 participates in DNA damage remains largely unknown. Here we present evidence that SMCHD1 recruitment to DNA damage foci is regulated by 53BP1. Knocking out SMCHD1 led to aberrant γH2AX foci accumulation and compromised cell survival upon DNA damage, demonstrating the critical role of SMCHD1 in DNA damage repair. Following DNA damage induction, SMCHD1 depletion resulted in reduced 53BP1 foci and increased BRCA1 foci, as well as less efficient non-homologous end joining (NHEJ) and elevated levels of homologous recombination (HR). Taken together, these results suggest an important function of SMCHD1 in promoting NHEJ and repressing HR repair in response to DNA damage.
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, SYSU-Baylor College of Medicine Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou, China, 510275 and.
authors.forename: Mengfan
authors.initials: M
authors.lastname: Tang
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, SYSU-Baylor College of Medicine Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou, China, 510275 and.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, SYSU-Baylor College of Medicine Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou, China, 510275 and.
authors.forename: Xiya
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, SYSU-Baylor College of Medicine Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou, China, 510275 and.
authors.forename: Tingting
authors.initials: T
authors.lastname: Deng
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, SYSU-Baylor College of Medicine Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou, China, 510275 and.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, SYSU-Baylor College of Medicine Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou, China, 510275 and mawenbin@mail.sysu.edu.cn.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
authors.affiliation: From the Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, SYSU-Baylor College of Medicine Joint Research Center for Biomedical Sciences, School of Life Sciences, Sun Yat-sen University, Guangzhou, China, 510275 and Verna and Marrs Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030 songyang@bcm.edu.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Songyang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D059766:DNA End-Joining Repair / Q000187:drug effects / Q000235:genetics*; D004273:DNA, Neoplasm / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D059767:Recombinational DNA Repair / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D000903:Antibiotics, Antineoplastic; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004273:DNA, Neoplasm; C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C578241:SMCHD1 protein, human; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D001761:Bleomycin; C105427:Zeocin
keywords: Cell Biology; DNA Damage; DNA Damage Response; DNA Recombination; DNA Repair; Signal Transduction