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Updated: Jul 19, 2025
06:24
Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
Published on: February 13, 2019
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FIRRM cooperates with FIGNL1 to promote RAD51 disassembly during DNA repair.
Edgar Pinedo-Carpio1,2, Julien Dessapt3,4, Adèle Beneyton3,4
1Lady Davis Institute for Medical Research, Segal Cancer Centre, Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine, Montréal, QC H3T 1E2, Canada.
Science Advances
|August 9, 2023
Summary
FIRRM promotes interstrand DNA cross-link (ICL) repair by resolving RAD51 foci at DNA double-strand breaks (DSBs). This protein has a FIGNL1-independent function in DNA repair, aiding cell survival after ICL damage.
Area of Science:
- Genetics
- Molecular Biology
- DNA Repair Mechanisms
Background:
- Interstrand DNA cross-links (ICLs) are complex DNA lesions that threaten genomic stability.
- Existing ICL repair pathways are known, but factors resolving ICL-induced DNA double-strand breaks (DSBs) are not fully understood.
Purpose of the Study:
- To identify novel factors involved in resolving ICL-induced DSBs.
- To elucidate the role of FIGNL1 interacting regulator of recombination and mitosis (FIRRM) in ICL repair.
Main Methods:
- CRISPR-based genomics screen to identify ICL sensitizers.
- Analysis of RAD51 foci resolution.
- In vitro DNA binding assays.
- Mafosfamide treatment to induce ICLs.
Main Results:
- FIRRM was identified as a sensitizer to mafosfamide, an ICL-inducing agent.
- FIRRM, similar to FIGNL1, aids in resolving RAD51 foci at ICL-induced DSBs.
- A stabilized FIRRM mutant (∆WCF) rescues RAD51 foci resolution and cell survival independently of FIGNL1.
- FIRRM exhibits preferential binding to single-stranded DNA in vitro.
Conclusions:
- FIRRM plays a crucial role in promoting interstrand DNA cross-link repair.
- FIRRM possesses a FIGNL1-independent function in DNA repair, potentially by directly facilitating RAD51 disassembly.
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