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

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00639711" target="_blank" >RIV/61388963:_____/25:00639711 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10503961 RIV/00216208:11310/25:10503961
Result on the web
<a href="https://doi.org/10.1038/s42003-025-08769-3" target="_blank" >https://doi.org/10.1038/s42003-025-08769-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s42003-025-08769-3" target="_blank" >10.1038/s42003-025-08769-3</a>

Result language
angličtina
Original language name
Mechanistic insights into alcohol-induced DNA crosslink repair by Slx4-Xpf-Ercc1 nuclease complex in the Fanconi anaemia pathway
Original language description
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. Moreover, SXE performs two precise incisions flanking the AA-ICL and can similarly repair a basic-site DNA interstrand crosslink. These results expand our understanding of how the FA pathway resolves alcohol-induced DNA damage. In addition, they suggest that SXE is a versatile nuclease complex and may be involved in repairing other types of crosslinks that may activate the FA pathway.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/GA24-12306S" target="_blank" >GA24-12306S: Elucidating the molecular mechanisms of DNA crosslink repair by replication-coupled DNA repair</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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