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

J 2024

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

ISIK, Esin, Kaustubh SHUKLA, Michaela POSPÍŠILOVÁ, Christiane KÖNIG, Martin ANDRS et. al.

Základní údaje

Originální název

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

Autoři

ISIK, Esin, Kaustubh SHUKLA, Michaela POSPÍŠILOVÁ (203 Česká republika, domácí), Christiane KÖNIG, Martin ANDRS, Satyajeet RAO, Vinicio ROSANO, Jana DOBROVOLNA (203 Česká republika), Lumír KREJČÍ (203 Česká republika, domácí) a Pavel JANSCAK (203 Česká republika)

Vydání

Science advances, WASHINGTON, AMER ASSOC ADVANCEMENT SCIENCE, 2024, 2375-2548

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 13.600 v roce 2022

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1126/sciadv.adk2685

UT WoS

001190871400013

Klíčová slova anglicky

MutSβ-MutLβ-FANCJ; DNA replication

Štítky

14110513, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 7. 2024 13:43, Mgr. Tereza Miškechová

Anotace

V originále

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

Návaznosti

GX21-22593X, projekt VaV

Název: Identifikace a charakterizace proteinů zahrnutých v metabolismu G-kvadruplexů a R-smyček a jejich vztah k replikaci DNA

Citovat

ISIK, Esin, Kaustubh SHUKLA, Michaela POSPÍŠILOVÁ, Christiane KÖNIG, Martin ANDRS, Satyajeet RAO, Vinicio ROSANO, Jana DOBROVOLNA, Lumír KREJČÍ a Pavel JANSCAK. MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops. Science advances. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE, 2024, roč. 10, č. 6, s. 1-16. ISSN 2375-2548. Dostupné z: https://dx.doi.org/10.1126/sciadv.adk2685.

@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 a 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, roč.~10, č.~6, s.~1-16. ISSN~2375-2548. Dostupné z: https://dx.doi.org/10.1126/sciadv.adk2685.

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