MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00616970" target="_blank" >RIV/68378050:_____/24:00616970 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/24:00135721 RIV/00159816:_____/24:00081393

Výsledek na webu

<a href="https://www.science.org/doi/10.1126/sciadv.adk2685" target="_blank" >https://www.science.org/doi/10.1126/sciadv.adk2685</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/sciadv.adk2685" target="_blank" >10.1126/sciadv.adk2685</a>

Jazyk výsledku

angličtina

Název v původním jazyce

MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops

Popis výsledku v původním jazyce

Transcription-replication conflicts (TRCs) induce formation of cotranscriptional RNA:DNA hybrids (R-loops) stabilized by G-quadruplexes (G4s) on the displaced DNA strand, which can cause fork stalling. Although it is known that these stalled forks can resume DNA synthesis in a process initiated by MUS81 endonuclease, how TRC-associated G4/R-loops are removed to allow fork passage remains unclear. Here, we identify the mismatch repair protein MutS beta, an MLH1-PMS1 heterodimer termed MutL beta, and the G4-resolving helicase FANCJ as factors that are required for MUS81-initiated restart of DNA replication at TRC sites in human cells. This DNA repair process depends on the G4-binding activity of MutS beta, the helicase activity of FANCJ, and the binding of FANCJ to MLH1. Furthermore, we show that MutS beta, MutL beta, and MLH1-FANCJ interaction mediate FANCJ recruitment to G4s. These data suggest that MutS beta, MutL beta, and FANCJ act in conjunction to eliminate G4/R-loops at TRC sites, allowing replication restart.

Název v anglickém jazyce

MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops

Popis výsledku anglicky

Transcription-replication conflicts (TRCs) induce formation of cotranscriptional RNA:DNA hybrids (R-loops) stabilized by G-quadruplexes (G4s) on the displaced DNA strand, which can cause fork stalling. Although it is known that these stalled forks can resume DNA synthesis in a process initiated by MUS81 endonuclease, how TRC-associated G4/R-loops are removed to allow fork passage remains unclear. Here, we identify the mismatch repair protein MutS beta, an MLH1-PMS1 heterodimer termed MutL beta, and the G4-resolving helicase FANCJ as factors that are required for MUS81-initiated restart of DNA replication at TRC sites in human cells. This DNA repair process depends on the G4-binding activity of MutS beta, the helicase activity of FANCJ, and the binding of FANCJ to MLH1. Furthermore, we show that MutS beta, MutL beta, and MLH1-FANCJ interaction mediate FANCJ recruitment to G4s. These data suggest that MutS beta, MutL beta, and FANCJ act in conjunction to eliminate G4/R-loops at TRC sites, allowing replication restart.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Science Advances

ISSN

2375-2548

e-ISSN

2375-2548

Svazek periodika

10

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

eadk2685

Kód UT WoS článku

001190871400013

EID výsledku v databázi Scopus

2-s2.0-85184737786