title: PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination.
abstract: If replication forks are perturbed, a multifaceted response including several DNA repair and cell cycle checkpoint pathways is activated to ensure faithful DNA replication. Here, we show that poly(ADP-ribose) polymerase 1 (PARP1) binds to and is activated by stalled replication forks that contain small gaps. PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA. Both PARP1 and PARP2 are required for hydroxyurea-induced homologous recombination to promote cell survival after replication blocks. Together, our data suggest that PARP1 and PARP2 detect disrupted replication forks and attract Mre11 for end processing that is required for subsequent recombination repair and restart of replication forks.
authors.affiliation: The Institute for Cancer Studies, University of Sheffield, Sheffield, UK.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Bryant
authors.forename: Eva
authors.initials: E
authors.lastname: Petermann
authors.forename: Niklas
authors.initials: N
authors.lastname: Schultz
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Jemth
authors.forename: Olga
authors.initials: O
authors.lastname: Loseva
authors.forename: Natalia
authors.initials: N
authors.lastname: Issaeva
authors.forename: Fredrik
authors.initials: F
authors.lastname: Johansson
authors.forename: Serena
authors.initials: S
authors.lastname: Fernandez
authors.forename: Peter
authors.initials: P
authors.lastname: McGlynn
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011995:Recombination, Genetic / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011065:Poly(ADP-ribose) Polymerases