{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shimada K"],"funding":["Swiss National Science Foundation"],"pagination":["9908"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11568337"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Combinational therapies provoking cell death are of major interest in oncology. Combining TORC2 kinase inhibition with the radiomimetic drug Zeocin results in a rapid accumulation of double-strand breaks (DSB) in the budding yeast genome. This lethal Yeast Chromosome Shattering (YCS) requires conserved enzymes of base excision repair. YCS can be attenuated by eliminating three N-glycosylases or endonucleases Apn1/Apn2 and Rad1, which act to convert oxidized bases into abasic sites and single-strand nicks. Adjacent lesions must be repaired in a step-wise fashion to avoid generating DSBs. Artificially increasing nuclear actin by destabilizing cytoplasmic actin filaments or by expressing a nuclear export-deficient actin interferes with this step-wise repair and generates DSBs, while mutants t"],"journal":["Nature communications"],"pubmed_title":["TORC2 inhibition triggers yeast chromosome fragmentation through misregulated Base Excision Repair of clustered oxidation events."],"pmcid":["PMC11568337"],"funding_grant_id":["176286","31003A_176286"],"pubmed_authors":["van Loon B","Bregenhorn S","Roth G","Tarashev CVD","Hurst V","Gasser SM","Gerhold CB","Helliwell SB","Shimada K","Jiricny J"],"additional_accession":[]},"is_claimable":false,"name":"TORC2 inhibition triggers yeast chromosome fragmentation through misregulated Base Excision Repair of clustered oxidation events.","description":"Combinational therapies provoking cell death are of major interest in oncology. Combining TORC2 kinase inhibition with the radiomimetic drug Zeocin results in a rapid accumulation of double-strand breaks (DSB) in the budding yeast genome. This lethal Yeast Chromosome Shattering (YCS) requires conserved enzymes of base excision repair. YCS can be attenuated by eliminating three N-glycosylases or endonucleases Apn1/Apn2 and Rad1, which act to convert oxidized bases into abasic sites and single-strand nicks. Adjacent lesions must be repaired in a step-wise fashion to avoid generating DSBs. Artificially increasing nuclear actin by destabilizing cytoplasmic actin filaments or by expressing a nuclear export-deficient actin interferes with this step-wise repair and generates DSBs, while mutants t","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-07-17T00:06:00.112Z","creation":"2025-04-03T23:23:46.129Z"},"accession":"S-EPMC11568337","cross_references":{"pubmed":["39548071"],"doi":["10.1038/s41467-024-54142-z"]}}