{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:17:25Z","timestamp":1788157045665,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01ES029520"],"award-info":[{"award-number":["U01ES029520"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01CA092584"],"award-info":[{"award-number":["P01CA092584"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP1OD006422"],"award-info":[{"award-number":["DP1OD006422"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ribonucleotides can serve as a strand discrimination signal in reconstituted in vitro biochemical mismatch repair (MMR) assays, but the influence of ribonucleotides on mismatch correction has not been measured directly\u00a0in vivo. We have developed a fluorescence-based host cell reactivation assay that reports correction of a mismatch in proximity of a site-specifically incorporated ribonucleotide. A ribonucleotide leads to enhanced mismatch correction. While neither inactivation of a single allele nor knockdown of RNaseH2 is sufficient to suppress ribonucleotide directed MMR, a modest but statistically significant impairment for repair of mismatches in the presence of an embedded ribonucleotide is observed in RNaseH2 knockout cell lines. Reporter plasmids with ribonucleotides located in either the 3\u2032 or 5\u2032 orientation are robustly repaired in MMR-proficient cells but are weakly repaired in MMR-deficient cells, underscoring their utility as effective MMR reporters. Significant ribonucleotide-enhanced mismatch correction was consistently observed in MMR-deficient cells when the ribonucleotide is in the 3\u2032 orientation. The presence of a ribonucleotide led to enhanced MMR even in RNaseH2 knockout cells, suggesting that other enzymes may promote ribonucleotide-directed MMR. Loss of RNaseH2 was not sufficient to confer significant resistance to the alkylating agent, temozolomide, in support of a model in which ribonucleotide-directed repair events make minor contributions to the canonical MMR pathway in mammalian cells. We propose a model in which MMR-independent ribonucleotide enhanced correction of mismatches can proceed by ribonucleotide excision repair when the ribonucleotide is in the 5\u2032 direction, and proceeds by an unknown mechanism when the ribonucleotide is in the 3\u2032 direction.<\/jats:p>","DOI":"10.1093\/nar\/gkag814","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T11:49:31Z","timestamp":1786189771000},"source":"Crossref","is-referenced-by-count":0,"title":["Fluorescent reporter assay reveals ribonucleotides promote mismatch correction\n                    <i>in vivo<\/i>"],"prefix":"10.1093","volume":"54","author":[{"given":"Sophie","family":"Erlich","sequence":"first","affiliation":[{"name":"Department of Environmental Health, Harvard T.H. Chan School of Public Health , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Mazzucato","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, MA 02139 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-2302","authenticated-orcid":false,"given":"Daniel J","family":"Laverty","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lehigh University , Bethlehem, PA 18018, United States\u00a0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leona D","family":"Samson","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, MA 02139 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2104-2093","authenticated-orcid":false,"given":"Zachary D","family":"Nagel","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T.H. 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