{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T11:22:59Z","timestamp":1772018579530,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T00:00:00Z","timestamp":1594080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103639"],"award-info":[{"award-number":["P20GM103639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008937","name":"OU College of Medicine Alumni Association","doi-asserted-by":"publisher","award":["C5112501"],"award-info":[{"award-number":["C5112501"]}],"id":[{"id":"10.13039\/100008937","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>It was recently shown that the 5\u2019 to 3\u2019 exoribonuclease XRN2 is involved in the DNA damage response. Importantly, loss of XRN2 abrogates DNA double stranded break repair via the non-homologous end-joining pathway. However, the mechanistic details of how XRN2 functions in the non-homologous end-joining repair process are unknown. In this study, we elucidated that XRN2-mediated RNA:DNA hybrid resolution is required to allow Ku70 binding to DNA ends. These data suggest that XRN2 is required for the initiation of non-homologous end-joining repair. Interestingly, we uncovered a role for XRN2 in the homologous recombination repair pathway. Loss of XRN2 lead to a decrease in the repair of double strand breaks by homologous recombination. Strikingly, when we removed RNA:DNA hybrids by RNaseH1 over-expression, homologous recombination was not restored. We found RNA:DNA hybrid formation at and downstream of the DSB site, suggesting that unregulated transcription inhibits homologous recombination repair. In summary, our results indicate a relation between RNA:DNA hybrid resolution and double strand break repair pathway choice.<\/jats:p>","DOI":"10.3390\/cancers12071821","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T10:41:09Z","timestamp":1594118469000},"page":"1821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["XRN2 Links RNA:DNA Hybrid Resolution to Double Strand Break Repair Pathway Choice"],"prefix":"10.3390","volume":"12","author":[{"given":"Tuyen T.","family":"Dang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA"}]},{"given":"Julio C.","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stephenson Cancer Center, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/35044005","article-title":"The DNA damage response: Putting checkpoints in perspective","volume":"408","author":"Zhou","year":"2000","journal-title":"Nature"},{"key":"ref_2","unstructured":"Donev, R. 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