{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:51:22Z","timestamp":1791453082717,"version":"4.3.3"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI64693"],"award-info":[{"award-number":["AI64693"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycobacterial UvrD1 is a DNA-dependent ATPase motor that participates as a monomer in nucleotide excision repair (NER). UvrD1 per se is a feeble helicase and its helicase activity is not required for NER. UvrD1, like other superfamily-1 ATPases, consists of 1A and 2A domains that engage ATP\u2022Mg2+. The 2A domain is punctuated by an inserted 2B domain that has been proposed to either couple ATP hydrolysis to duplex unwinding or function as an autoinhibitor of unwinding that is overcome by homodimerization. Here, we designed and characterized UvrD1-\u22062B, in which the entire 2B domain is internally deleted, that enabled an evaluation of the role of the 2B domain in UvrD1 function. Removal of the 2B domain elicited a gain of helicase activity, thereby implicating the 2B domain as an impediment to UvrD1\u2019s latent duplex unwinding capacity. We report that (i) UvrD1-\u22062B is unable to fulfill UvrD1\u2019s role in NER; (ii) a merodiploid uvrD1+ \u00a0uvrD1-\u22062B strain is as defective in NER as a \u2206uvrD1 strain; and (iii) inducible overexpression of uvrD1-\u22062B in wild-type cells slows growth. The latter two effects of UvrD1-\u22062B are eliminated by an ATPase\/helicase-inactivating mutation. We surmise that unbridled UvrD1 helicase activity is detrimental to mycobacterial physiology.<\/jats:p>","DOI":"10.1093\/nar\/gkag958","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:21:54Z","timestamp":1790335314000},"source":"Crossref","is-referenced-by-count":0,"title":["Deleting the 2B domain of mycobacterial UvrD1 unmasks a latent helicase activity\n                    <i>in vitro<\/i>\n                    but effaces UvrD1 activity in nucleotide excision repair\n                    <i>in vivo<\/i>"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9949-309X","authenticated-orcid":false,"given":"Garrett M","family":"Warren","sequence":"first","affiliation":[{"name":"Molecular Biology Program, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5034-6438","authenticated-orcid":false,"given":"Stewart","family":"Shuman","sequence":"additional","affiliation":[{"name":"Molecular Biology Program, Memorial Sloan Kettering Cancer Center , New York, NY 10065,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"2026100805080290000_B1","doi-asserted-by":"publisher","first-page":"a012591","DOI":"10.1101\/cshperspect.a012591","article-title":"Prokaryotic nucleotide excision repair","volume":"5","author":"Kisker","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2026100805080290000_B2","doi-asserted-by":"publisher","first-page":"17374","DOI":"10.1074\/jbc.AC120.016325","article-title":"Mycobacteria excise DNA damage in 12- or 13-nucleotide-long oligomers by prokaryotic-type dual incisions and performs transcription-coupled repair","volume":"295","author":"Selby","year":"2020","journal-title":"J Biol Chem"},{"key":"2026100805080290000_B3","doi-asserted-by":"publisher","first-page":"4581","DOI":"10.1128\/IAI.73.8.4581-4587.2005","article-title":"Role for nucleotide excision repair in virulence of Mycobacterium tuberculosis","volume":"73","author":"Darwin","year":"2005","journal-title":"Infect Immun"},{"key":"2026100805080290000_B4","doi-asserted-by":"publisher","first-page":"2916","DOI":"10.1128\/JB.06654-11","article-title":"Important role for Mycobacterium tuberculosis UvrD1 in pathogenesis and persistence apart from its function in nucleotide excision repair","volume":"194","author":"Houghton","year":"2012","journal-title":"J Bacteriol"},{"key":"2026100805080290000_B5","doi-asserted-by":"publisher","first-page":"15114","DOI":"10.1074\/jbc.M701167200","article-title":"Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair","volume":"282","author":"Sinha","year":"2007","journal-title":"J Biol Chem"},{"key":"2026100805080290000_B6","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/nsmb915","article-title":"Mechanism of nonhomologous end-joining in mycobacteria: a low fidelity repair system driven by Ku, ligase D and ligase C","volume":"12","author":"Gong","year":"2005","journal-title":"Nat Struct Mol Biol"},{"key":"2026100805080290000_B7","doi-asserted-by":"publisher","first-page":"168367","DOI":"10.1016\/j.jmb.2023.168367","article-title":"Mycobacterium tuberculosis Ku stimulates multi-round DNA unwinding by UvrD1 monomers","volume":"436","author":"Chadda","year":"2024","journal-title":"J Mol Biol"},{"key":"2026100805080290000_B8","doi-asserted-by":"publisher","first-page":"4019","DOI":"10.1021\/bi900103d","article-title":"Mutational analysis of Mycobacterium UvrD1 identifies functional groups required for ATP hydrolysis, DNA unwinding, and chemomechanical 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