The FANCD2-FANCI heterodimer coordinates chromatin openness and cell cycle progression throughout DNA double-strand break repair.

ABSTRACT: The FANCD2-FANCI heterodimer contributes to DNA repair at interstrand crosslinks and sites of replication stress. This complex has been physically and mechanistically linked to double-strand break (DSB) repair, but its role in that process remains undefined. Here, we show that the FANCD2-FANCI heterodimer dynamically interacts with open chromatin regions, including transient DSB-induced open chromatin, where it can be stabilized through co-activation by the DNA repair kinase ATM and the Fanconi anemia core ubiquitin ligase. The loaded FANCD2-FANCI heterodimer stabilizes open chromatin and promotes resection and loading of RPA through increased association of BRCA1 and BLM. Chromatin-loaded FANCD2-FANCI has a second, distinct function promoting a G2 cell cycle arrest that is dependent on th

SUBMITTER: Joyce CM 

PROVIDER: S-EPMC12934461 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature