{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317741/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317741"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"DNA-contact mutant p53 displaces BRCA2 from chromatin and drives R-loop associated genome instability [CUT&Tag]","description":"Accumulating evidence underscores the role of p53 mutations in inducing genomic instability, yet the underlying mechanisms remain largely elusive. Our study reveals that the p53-R273H mutation leads to the accumulation of R-loops. Specifically, p53-R273H forms abnormal condensates with BRCA2, impairing the chromatin binding of BRCA2, thereby inhibiting R-loop resolution and contributing to genomic instability. Furthermore, we have identified DDX3X as a pivotal downstream effector in the p53-BRCA2 pathway, responsible for dissolving R-loops. Notably, the strategic combination of a DDX3X inhibitor with a PARP inhibitor exhibits a potent synergistic effect, enhancing the sensitivity of cancer cell lines harboring the p53-R273H mutation. These findings uncover exploitable vulnerabilities in tumors carrying this specific p53 mutation, presenting promising opportunities for targeted therapeutic intervention.","dates":{"publication":"2026/05/21"},"accession":"GSE317741","cross_references":{"GSM":["GSM9477496","GSM9477497","GSM9477498"],"GPL":["34281"],"GSE":["317741"],"taxon":["Homo sapiens"]}}