MutSß-MutLß-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops.
Sci Adv
; 10(6): eadk2685, 2024 Feb 09.
Article
em En
| MEDLINE
| ID: mdl-38324687
ABSTRACT
Transcription-replication conflicts (TRCs) induce formation of cotranscriptional RNADNA 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 MutSß, an MLH1-PMS1 heterodimer termed MutLß, 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 MutSß, the helicase activity of FANCJ, and the binding of FANCJ to MLH1. Furthermore, we show that MutSß, MutLß, and MLH1-FANCJ interaction mediate FANCJ recruitment to G4s. These data suggest that MutSß, MutLß, and FANCJ act in conjunction to eliminate G4/R-loops at TRC sites, allowing replication restart.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Grupos de Complementação da Anemia de Fanconi
/
Estruturas R-Loop
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article