1. Academic Validation
  2. C1orf112 teams up with FIGNL1 to facilitate RAD51 filament disassembly and DNA interstrand cross-link repair

C1orf112 teams up with FIGNL1 to facilitate RAD51 filament disassembly and DNA interstrand cross-link repair

  • Cell Rep. 2023 Jul 28;42(8):112907. doi: 10.1016/j.celrep.2023.112907.
Zenan Zhou 1 Han Yang 1 Xinxin Liang 1 Tao Zhou 1 Tao Zhang 1 Yang Yang 2 Jiadong Wang 3 Weibin Wang 4
Affiliations

Affiliations

  • 1 Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
  • 2 Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
  • 3 Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: wangjd@bjmu.edu.cn.
  • 4 Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: weibinwang@bjmu.edu.cn.
Abstract

The recombinase RAD51 plays a core role in DNA repair by homologous recombination (HR). The assembly and disassembly of RAD51 filament need to be orderly regulated by mediators such as BRCA2 and anti-recombinases. To screen for potential regulators of RAD51, we perform RAD51 proximity proteomics and identify factor C1orf112. We further find that C1orf112 complexed with FIGNL1 facilitates RAD51 filament disassembly in the HR step of Fanconi anemia (FA) pathway. Specifically, C1orf112 physically interacts with FIGNL1 and enhances its protein stability. Meanwhile, the RAD51 filament disassembly activity of FIGNL1 is directly stimulated by C1orf112. BRCA2 directly interacts with C1orf112-FIGNL1 complex and functions upstream of this complex to protect RAD51 filament from premature disassembly. C1orf112- and FIGNL1-deficient cells are primarily sensitive to DNA interstrand cross-link (ICL) agents. Thus, these findings suggest an important function of C1orf112 in RAD51 regulation in the HR step of ICL repair by FA pathway.

Keywords

BRCA2; C1orf112; CP: Molecular biology; DNA damage repair; DNA interstrand cross-link; FIGNL1; Fanconi anemia pathway; RAD51 filament; homologous recombination.

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