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

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.