Publication highlights

Fignl1 is an essential gene in mice and mutations have been found in various cancers and genetic disorders. FIGNL1 plays critical roles in maintaining genome stability via modulating RAD51 recombinase, a key protein in repairing DNA and maintaining genome integrity. In collaboration with Marin Jasin in Sloan Memorial Kettering Cancer Center, researchers at the Crick reveal that FIGNL1 prevents RAD51 chromatin accumulation under normal conditions as well as under DNA damaging conditions, and this is responsible for its essential activity in cell viability. CryoEM structure and comprehensive in vitro and in vivo studies reveal a unique mechanistic model for RAD51 dissociation where FIGNL1, a molecular motor, encloses and pulls RAD51 into its structure, leading to RAD51 remodeling and dissociation from chromatin. This unique mode suggests that FIGNL1 can dissociate RAD51 from many bound substrates, including DNA and nucleosomes and account for its vitality in cellular activities.