# The INO80 chromatin remodeller facilitates DNA damage bypass via postreplicative gap repair

## TL;DR

The INO80 complex helps repair DNA damage during replication by aiding in the repair of gaps in the daughter DNA strand.

## Contribution

The study identifies a new role for INO80 in DNA damage bypass through postreplicative gap repair, independent of its other functions.

## Key findings

- INO80 promotes Exo1-dependent expansion of daughter-strand gaps during DNA repair.
- Its role in gap repair is distinct from its function in double-strand break repair.
- INO80 facilitates access to the boundaries of DNA gaps to aid repair processes.

## Abstract

Chromatin remodellers play a crucial role in transcription, replication and genome maintenance by dynamically regulating the accessibility of DNA. The INO80 complex contributes to multiple aspects of DNA repair and DNA replication stress management. It primarily facilitates nucleosome sliding and has been linked to the removal of the histone variant H2A.Z from chromatin. Our study demonstrates that the INO80 complex promotes DNA damage bypass through postreplicative daughter-strand gap repair. The complex acts downstream of PCNA ubiquitylation, enabling both Exo1-dependent gap expansion and gap filling via translesion synthesis or template switching. Importantly, its function in DNA damage bypass is independent of H2A.Z exchange and separable from its roles in DNA double-strand break repair and transcriptional regulation. Instead, it is consistent with a ruler-like activity that ensures proper nucleosome positioning around both ends of daughter-strand gaps, providing access to exonucleases and DNA polymerases involved in gap processing. These findings underscore the importance of the INO80 complex in facilitating access to damaged DNA regions for timely and effective repair.

The INO80 chromatin remodelling complex has various roles in genome maintenance, acting via nucleosome sliding and H2A.Z removal. Here, it is shown to also facilitate the bypass of DNA lesions during genome replication by promoting the repair of damage-induced daughter-strand gaps.

INO80 promotes postreplicative DNA damage bypass at daughter-strand gaps.INO80 promotes Exo1-dependent expansion of daughter-strand gaps.INO80’s function in gap repair is independent of its role in double-strand break repair.INO80 may promote gap repair by facilitating access to the boundaries of the gap.

INO80 promotes postreplicative DNA damage bypass at daughter-strand gaps.

INO80 promotes Exo1-dependent expansion of daughter-strand gaps.

INO80’s function in gap repair is independent of its role in double-strand break repair.

INO80 may promote gap repair by facilitating access to the boundaries of the gap.

A novel INO80 function in gap repair involves Exo1-dependent expansion of daughter-strand gaps and is independent of its role in double-strand break repair.