| http://purl.uniprot.org/citations/37697435 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/37697435 | http://www.w3.org/2000/01/rdf-schema#comment | "Breast cancer linked with BRCA1/2 mutations commonly recur and resist current therapies, including PARP inhibitors. Given the lack of effective targeted therapies for BRCA1-mutant cancers, we sought to identify novel targets to selectively kill these cancers. Here, we report that loss of RNF8 significantly protects Brca1-mutant mice against mammary tumorigenesis. RNF8 deficiency in human BRCA1-mutant breast cancer cells was found to promote R-loop accumulation and replication fork instability, leading to increased DNA damage, senescence, and synthetic lethality. Mechanistically, RNF8 interacts with XRN2, which is crucial for transcription termination and R-loop resolution. We report that RNF8 ubiquitylates XRN2 to facilitate its recruitment to R-loop-prone genomic loci and that RNF8 deficiency in BRCA1-mutant breast cancer cells decreases XRN2 occupancy at R-loop-prone sites, thereby promoting R-loop accumulation, transcription-replication collisions, excessive genomic instability, and cancer cell death. Collectively, our work identifies a synthetic lethal interaction between RNF8 and BRCA1, which is mediated by a pathological accumulation of R-loops."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.org/dc/terms/identifier | "doi:10.1093/nar/gkad733"xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Arrowsmith C."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Hao J."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Raught B."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Miller J."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Pujana M.A."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Brown G.W."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Seitova A."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Saad A."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Masson J.Y."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Stewart G.S."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Krishnan R."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Mekhail K."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "St-Germain J."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Reynolds J.J."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Sanchez O."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Ho B."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Hakem R."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Hande M.P."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Alaoui-Jamali M."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Patel P.S."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Hakem A."xsd:string |
| http://purl.uniprot.org/citations/37697435 | http://purl.uniprot.org/core/author | "Nixon K.C.J."xsd:string |