GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE278nnn/GSE278484/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278484GEOGSEfalsep53 mutation hijacks BRCA2 to induce genomic instability [CUT&Tag ]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.2026/05/21GSE278484GSM8547484GSM8547486GSM854748524676278484Homo sapiens