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.

Basic information

Original name

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

Authors

ISIK, Esin, Kaustubh SHUKLA, Michaela POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Christiane KÖNIG, Martin ANDRS, Satyajeet RAO, Vinicio ROSANO, Jana DOBROVOLNA (203 Czech Republic), Lumír KREJČÍ (203 Czech Republic, belonging to the institution) and Pavel JANSCAK (203 Czech Republic)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 13.600 in 2022

Organization unit

Faculty of Medicine

DOI

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

UT WoS

001190871400013

Keywords in English

MutSβ-MutLβ-FANCJ; DNA replication

Abstract

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

Links

GX21-22593X, research and development project

Name: 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 and 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, vol. 10, No 6, p. 1-16. ISSN 2375-2548. Available from: 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 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.

Detailed Information on Publication Record