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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10503961 RIV/00216208:11310/25:10503961

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA24-12306S" target="_blank" >GA24-12306S: Objasnění molekulárních mechanismů opravy příčných vazeb v DNA vázané na replikaci DNA</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Communications Biology

ISSN

2399-3642

e-ISSN

2399-3642

Svazek periodika

8

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

1374

Kód UT WoS článku

001581791400001

EID výsledku v databázi Scopus

2-s2.0-105017417126