2. Academic Validation
  3. Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) promotes non-homologous end joining and inhibits homologous recombination repair upon DNA damage

Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) promotes non-homologous end joining and inhibits homologous recombination repair upon DNA damage

  • J Biol Chem. 2014 Dec 5;289(49):34024-32. doi: 10.1074/jbc.M114.601179.
Mengfan Tang 1,  Yujing Li 1,  Xiya Zhang 1,  Tingting Deng 1,  Zhifen Zhou 1,  Wenbin Ma 2,  Zhou Songyang 3
Affiliations

Affiliations

  • 1 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.
  • 2 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 [email protected].
  • 3 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 [email protected].
PMID: 25294876 DOI: 10.1074/jbc.M114.601179
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.

Keywords

Cell Biology; DNA Damage; DNA Damage Response; DNA Recombination; DNA Repair; Signal Transduction.

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