{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dong Q"],"funding":["MEXT | Japan Society for the Promotion of Science","MEXT | Japan Society for the Promotion of Science (JSPS)","Cancer Research UK"],"pagination":["5820"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12214830"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["RIF1 is a multifunctional protein that regulates DNA replication and repair. RIF1-deficient cells are hypersensitive to DNA replication stress. Of the two alternatively spliced RIF1 isoforms, called RIF1-Short and RIF1-Long, the RIF1-Long isoform is more capable than RIF1-Short in supporting cell recovery from replication stress. Examining replication stress resistance mechanisms specific to RIF1-Long, we find that prolonged replication stress unexpectedly induces interaction of RIF1-Long with BRCA1. Mechanistically, a phosphorylated SPKF motif unique to the RIF1-Long isoform binds the tandem BRCT domain of BRCA1. BRCA1-RIF1-Long interaction is strongly down-regulated through dephosphorylation by RIF1-associated Protein Phosphatase 1. BRCA1-RIF1-Long interaction requires ATR signaling, and occurs predominantly during S phase. Loss of RIF1-Long impairs the formation of RAD51 foci, and reduces the efficiency of homology-mediated repair at broken replication forks. In summary, our investigation establishes RIF1-Long as a new functional binding partner of the BRCA1-BRCT domain, crucial to protect cells from extended DNA replication stress by enabling RAD51-dependent repair of broken replication forks."],"journal":["Nature communications"],"pubmed_title":["The human RIF1-Long isoform interacts with BRCA1 to promote recombinational fork repair under DNA replication stress."],"pmcid":["PMC12214830"],"funding_grant_id":["DRCPGM\\100013","C1445/A19059","JP21H0419","JP23H04925","C302/A24386"],"pubmed_authors":["Hiraga SI","Day M","Oliver AW","Saito Y","Watts LP","Pearl LH","Donaldson AD","Parker E","Dong Q","Kanemaki MT"],"additional_accession":[]},"is_claimable":false,"name":"The human RIF1-Long isoform interacts with BRCA1 to promote recombinational fork repair under DNA replication stress.","description":"RIF1 is a multifunctional protein that regulates DNA replication and repair. RIF1-deficient cells are hypersensitive to DNA replication stress. Of the two alternatively spliced RIF1 isoforms, called RIF1-Short and RIF1-Long, the RIF1-Long isoform is more capable than RIF1-Short in supporting cell recovery from replication stress. Examining replication stress resistance mechanisms specific to RIF1-Long, we find that prolonged replication stress unexpectedly induces interaction of RIF1-Long with BRCA1. Mechanistically, a phosphorylated SPKF motif unique to the RIF1-Long isoform binds the tandem BRCT domain of BRCA1. BRCA1-RIF1-Long interaction is strongly down-regulated through dephosphorylation by RIF1-associated Protein Phosphatase 1. BRCA1-RIF1-Long interaction requires ATR signaling, and occurs predominantly during S phase. Loss of RIF1-Long impairs the formation of RAD51 foci, and reduces the efficiency of homology-mediated repair at broken replication forks. In summary, our investigation establishes RIF1-Long as a new functional binding partner of the BRCA1-BRCT domain, crucial to protect cells from extended DNA replication stress by enabling RAD51-dependent repair of broken replication forks.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-06-01T15:31:20.761Z","creation":"2026-04-08T13:42:20.383Z"},"accession":"S-EPMC12214830","cross_references":{"pubmed":["40595496"],"doi":["10.1038/s41467-025-60817-y"]}}