RAD51 separation of function mutation maintenance but preserves DSB repair

• Autoři: SON Mi Young; BELÁŇ Ondrej; ŠPÍREK Mário; CIBULKA Jakub; NIKULENKOV Fedor; KIM You Young; HWANG Sunyoung; MYUNG Kyungjae; MONTAGNA Cristina; KIM Tae Moon; KREJČÍ Lumír; HASTY Paul
• Rok publikování: 2024
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: iScience
• Fakulta / Pracoviště MU: Lékařská fakulta
• www: https://doi.org/10.1016/j.isci.2024.109524
• Doi: http://dx.doi.org/10.1016/j.isci.2024.109524
• Klíčová slova: Properties of biomolecules; Genetics; Molecular biology; Molecular interaction
• Popis: Homologous recombination (HR) protects replication forks (RFs) and repairs DNA double-strand breaks (DSBs). Within HR, BRCA2 regulates RAD51 via two interaction regions: the BRC repeats to form filaments on single-stranded DNA and exon 27 (Ex27) to stabilize the filament. Here, we identified a RAD51 S181P mutant that selectively disrupted the RAD51-Ex27 association while maintaining interaction with BRC repeat and proficiently forming filaments capable of DNA binding and strand invasion. Interestingly, RAD51 S181P was defective for RF protection/restart but proficient for DSB repair. Our data suggest that Ex27-mediated stabilization of RAD51 filaments is required for the protection of RFs, while it seems dispensable for the repair of DSBs.

Související projekty

• Identification and characterization of proteins involved in metabolism of G-quadruplexes and R-loops and molecular mechanisms of their relationship with replication