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

## TL;DR

The FANCD2-FANCI complex helps repair DNA breaks by stabilizing open chromatin and coordinating cell cycle arrest.

## Contribution

The study reveals a two-step role of FANCD2-FANCI in DNA repair and cell cycle regulation.

## Key findings

- FANCD2-FANCI binds to open chromatin regions near DNA double-strand breaks.
- The complex promotes DNA repair by stabilizing chromatin and recruiting repair factors like BRCA1 and BLM.
- FANCD2-FANCI also induces G2 cell cycle arrest via the ATR-CHK1-WEE1 pathway.

## 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 the ATR-CHK1-WEE1 axis. Our results support a two-step genome surveillance model in which FANCD2-FANCI monitors open chromatin sites and is stably loaded to coordinate DNA repair activities in response to signaling from a DNA repair kinase.

Joyce et al. demonstrate that the FANCD2-FANCI heterodimer binds to open chromatin, including transiently accessible regions formed near double-strand breaks. Chromatin-loaded FANCD2-FANCI promotes DNA repair activities in the vicinity of double-strand breaks.