{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:34:11Z","timestamp":1781732051530,"version":"3.54.5"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"20","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK057808"],"award-info":[{"award-number":["DK057808"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Repeat Expansion Diseases, a large group of human diseases that includes the fragile X-related disorders (FXDs) and Huntington's disease (HD), all result from expansion of a disease-specific microsatellite via a mechanism that is not fully understood. We have previously shown that mismatch repair (MMR) proteins are required for expansion in a mouse model of the FXDs, but that the FANCD2 and FANCI associated nuclease 1 (FAN1), a component of the Fanconi anemia (FA) DNA repair pathway, is protective. FAN1\u2019s nuclease activity has been reported to be dispensable for protection against expansion in an HD cell model. However, we show here that in a FXD mouse model a point mutation in the nuclease domain of FAN1 has the same effect on expansion as a null mutation. Furthermore, we show that FAN1 and another nuclease, EXO1, have an additive effect in protecting against MSH3-dependent expansions. Lastly, we show that the loss of FANCD2, a vital component of the Fanconi anemia DNA repair pathway, has no effect on expansions. Thus, FAN1 protects against MSH3-dependent expansions without diverting the expansion intermediates into the canonical FA pathway and this protection depends on FAN1 having an intact nuclease domain.<\/jats:p>","DOI":"10.1093\/nar\/gkab899","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T13:12:33Z","timestamp":1634044353000},"page":"11643-11652","source":"Crossref","is-referenced-by-count":25,"title":["FAN1\u2019s protection against CGG repeat expansion requires its nuclease activity and is FANCD2-independent"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7281-3914","authenticated-orcid":false,"given":"Xiaonan","family":"Zhao","sequence":"first","affiliation":[{"name":"Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory Animal Sciences section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-0740","authenticated-orcid":false,"given":"Karen","family":"Usdin","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"2021111805161669600_B1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/B978-0-444-63233-3.00009-9","article-title":"Repeat expansion diseases","volume":"147","author":"Paulson","year":"2018","journal-title":"Handb. 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