{
  "id": 14852424,
  "title": "Global signatures of Ribonucleotide Excision Repair deficiency and its therapeutic vulnerabilities",
  "url": "https://urgent.news/2026/10/15/global-signatures-of-ribonucleotide-excision-repair-deficiency-and",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-15T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757935v1?rss=1"
  },
  "original_language": "en",
  "account": "Cancer treatments often exploit DNA repair deficiencies, but many states where these pathways are impaired remain undetectable due to a lack of biomarkers and gene-based diagnostic tools. Ribonucleotide excision repair (RER) is a pathway that corrects misincorporated ribonucleotides in genomic DNA. Scientists have now demonstrated that RER deficiency produces a unique genome-wide pattern of mutations, including insertion-deletion events, substitutions, and structural variations. To identify tumors with RER deficiency, the researchers created a tool called RERDetect, a whole-genome classifier. Applying RERDetect to over 11,000 primary and metastatic cancers, they found a subgroup of tumors with evidence of RER deficiency, with most of these cases showing no detectable genetic mutations in RNASEH2 genes. The scientists discovered that promoter hypermethylation of RNASEH2C was a common cause of RER inactivation. Cells deficient in RER displayed unique vulnerabilities, such as sensitivity to inhibition of the enzymes EXO1 and FANCM. These findings establish RER deficiency as a new, previously undetected DNA repair-deficient state in cancer, highlighting how distinct mutational signatures can reveal clinically relevant tumor phenotypes that conventional genomic diagnostics might miss.",
  "summary": "Cancer therapies increasingly exploit DNA repair deficiencies, yet many clinically actionable repair-deficient states remain undetectable because they lack robust biomarkers and are not identifiable through gene-based diagnostics. Here, we show that deficiency of ribonucleotide excision repair (RER), a pathway that removes misincorporated ribonucleotides from genomic DNA, generates a distinct…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}