{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kharat SS"],"funding":["National Institutes of Health National Cancer Institute","NIH"],"pagination":["110393"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12281170"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["301(7)"],"pubmed_abstract":["Mutations in BRCA1 and BRCA2 genes are the leading cause of hereditary breast and ovarian cancer. BRCA1/2-mutant cells are defective in repairing damaged DNA by homologous recombination and are characterized by hypersensitivity to PARP inhibitors. PARP inhibitors can trap PARP proteins on the chromatin, a mechanism that can contribute to the death of BRCA1/2-deficient cells. The FDA has approved multiple PARP inhibitors for the treatment of metastatic breast and ovarian cancers, yet despite the success of PARP inhibitors in treating BRCA1/2-mutant cancers, drug resistance is a major challenge. Here, we report that 5hmC enhances PARP1 trapping on the chromatin in olaparib-treated cells. Elevated PARP trapping generates replication gaps, leading to the restoration of PARP inhibitor sensitivi"],"journal":["The Journal of biological chemistry"],"pubmed_title":["5hmC enhances PARP trapping and restores PARP inhibitor sensitivity in chemoresistant BRCA1/2-deficient cells."],"pmcid":["PMC12281170"],"funding_grant_id":["R01 CA218315"],"pubmed_authors":["Fox SD","Mishra AP","Kharat SS","Dierman D","Sengodan SK","Chazin WJ","Sharan SK"],"additional_accession":[]},"is_claimable":false,"name":"5hmC enhances PARP trapping and restores PARP inhibitor sensitivity in chemoresistant BRCA1/2-deficient cells.","description":"Mutations in BRCA1 and BRCA2 genes are the leading cause of hereditary breast and ovarian cancer. BRCA1/2-mutant cells are defective in repairing damaged DNA by homologous recombination and are characterized by hypersensitivity to PARP inhibitors. PARP inhibitors can trap PARP proteins on the chromatin, a mechanism that can contribute to the death of BRCA1/2-deficient cells. The FDA has approved multiple PARP inhibitors for the treatment of metastatic breast and ovarian cancers, yet despite the success of PARP inhibitors in treating BRCA1/2-mutant cancers, drug resistance is a major challenge. Here, we report that 5hmC enhances PARP1 trapping on the chromatin in olaparib-treated cells. Elevated PARP trapping generates replication gaps, leading to the restoration of PARP inhibitor sensitivi","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-03-16T07:07:36.334Z","creation":"2025-08-17T03:05:47.226Z"},"accession":"S-EPMC12281170","cross_references":{"pubmed":["40543584"],"doi":["10.1016/j.jbc.2025.110393"]}}