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@article{2387597,
author = {Isik, Esin and Shukla, Kaustubh and Pospíšilová, Michaela and König, Christiane and Andrs, Martin and Rao, Satyajeet and Rosano, Vinicio and Dobrovolna, Jana and Krejčí, Lumír and Janscak, Pavel},
article_location = {WASHINGTON},
article_number = {6},
doi = {http://dx.doi.org/10.1126/sciadv.adk2685},
keywords = {MutSβ-MutLβ-FANCJ; DNA replication},
language = {eng},
issn = {2375-2548},
journal = {Science advances},
title = {MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops},
url = {https://www.science.org/doi/full/10.1126/sciadv.adk2685?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org},
volume = {10},
year = {2024}
}
TY - JOUR
ID - 2387597
AU - Isik, Esin - Shukla, Kaustubh - Pospíšilová, Michaela - König, Christiane - Andrs, Martin - Rao, Satyajeet - Rosano, Vinicio - Dobrovolna, Jana - Krejčí, Lumír - Janscak, Pavel
PY - 2024
TI - MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops
JF - Science advances
VL - 10
IS - 6
SP - 1-16
EP - 1-16
PB - AMER ASSOC ADVANCEMENT SCIENCE
SN - 23752548
KW - MutSβ-MutLβ-FANCJ
KW - DNA replication
UR - https://www.science.org/doi/full/10.1126/sciadv.adk2685?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org
N2 - 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 MutSβ, an MLH1-PMS1 heterodimer termed MutLβ, 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 MutSβ, the helicase activity of FANCJ, and the binding of FANCJ to MLH1. Furthermore, we show that MutSβ, MutLβ, and MLH1-FANCJ interaction mediate FANCJ recruitment to G4s. These data suggest that MutSβ, MutLβ, and FANCJ act in conjunction to eliminate G4/R-loops at TRC sites, allowing replication restart
ER -
ISIK, Esin, Kaustubh SHUKLA, Michaela POSPÍŠILOVÁ, Christiane KÖNIG, Martin ANDRS, Satyajeet RAO, Vinicio ROSANO, Jana DOBROVOLNA, Lumír KREJČÍ and Pavel JANSCAK. MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops. \textit{Science advances}. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE, 2024, vol.~10, No~6, p.~1-16. ISSN~2375-2548. Available from: https://dx.doi.org/10.1126/sciadv.adk2685.
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