Mechanistic insights into alcohol-induced DNA crosslink repair by Slx4-Xpf-Ercc1 nuclease complex in the Fanconi anaemia pathway.

ABSTRACT: Alcohol is broken down in the body into acetaldehyde, a toxic chemical that can damage DNA by creating interstrand crosslinks (AA-ICL). These crosslinks block DNA replication and threaten the stability of the genome. A rare genetic disease, Fanconi anaemia (FA), is marked by extreme sensitivity to DNA crosslinking agents, including acetaldehyde. Although the Fanconi anaemia DNA repair pathway is known to fix this type of damage, exactly how it repairs acetaldehyde crosslinks is not yet understood. Here we show that the FA nuclease Slx4-Xpf-Ercc1 (SXE) plays a key role in the repair of AA-ICL. Using a DNA replication fork with site-specific AA-ICL, we show that SXE specifically excises this crosslink, highlighting its role in the repair of alcohol-induced DNA interstrand crosslinks. Moreove

SUBMITTER: Havlikova J 

PROVIDER: S-EPMC12475018 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature