MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216224:14110/24:00135721 RIV/00159816:_____/24:00081393
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Science Advances
ISSN
2375-2548
e-ISSN
2375-2548
Volume of the periodical
10
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
eadk2685
UT code for WoS article
001190871400013
EID of the result in the Scopus database
2-s2.0-85184737786