{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:06:33Z","timestamp":1785434793563,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,21]]},"group-title":"Biochemistry","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R35 GM136632"],"award-info":[{"award-number":["R35 GM136632"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35 GM144282"],"award-info":[{"award-number":["R35 GM144282"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  DNA helicases are ATP-dependent motor proteins that catalyze duplex DNA unwinding and are involved in DNA repair, recombination and replication restart. Prominent members of the non-hexameric SF1A UvrD-family helicases are\n                  <jats:italic>E. coli<\/jats:italic>\n                  UvrD, Rep,\n                  <jats:italic>B. stearothermophilus<\/jats:italic>\n                  PcrA and\n                  <jats:italic>M. tuberculosis<\/jats:italic>\n                  UvrD1. SF1A monomers are processive 3\u2019 to 5\u2019 single stranded DNA translocases, but need to be activated to become DNA helicases. One mechanism of activation is dimerization. Whereas Rep, UvrD and PcrA form non-covalent dimers, the\n                  <jats:italic>Mtb<\/jats:italic>\n                  UvrD1 helicase forms a redox-dependent covalent dimer. Dimerization of\n                  <jats:italic>Mtb<\/jats:italic>\n                  UvrD1 occurs between the same regulatory domain (2B) within each subunit stabilized by a disulfide bond formed between the same cysteine (Cys451) within each subunit. Dimerization relieves an inhibitory interaction between the 2B domain and duplex DNA within the monomer-DNA complex. We show here that Rep, UvrD and PcrA dimerize using the same 2B-2B interface. By placing a Cys residue within the 2B domains of Rep, UvrD and PcrA in the structurally equivalent position occupied by Cys451 of\n                  <jats:italic>Mtb<\/jats:italic>\n                  UvrD1, all three enzymes form redox-dependent covalent dimers that are constitutively active helicases with increased processivity compared to the non-covalent dimers. Hence, the 2B domain is a general dimerization domain for UvrD-family SF1A helicases.\n                <\/jats:p>","DOI":"10.64898\/2026.05.20.726581","type":"posted-content","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T08:00:18Z","timestamp":1779436818000},"source":"Crossref","is-referenced-by-count":0,"title":["A Conserved Mechanism for Dimerization and Activation of Superfamily 1A UvrD-family Helicases"],"prefix":"10.64898","author":[{"given":"Binh","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis School of Medicine. 660 S. Euclid Ave., Box 8231. St. Louis, MO 63110-1093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kacey N.","family":"Mersch","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis School of Medicine. 660 S. Euclid Ave., Box 8231. St. Louis, MO 63110-1093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Chadda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis School of Medicine. 660 S. Euclid Ave., Box 8231. St. Louis, MO 63110-1093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4314-3215","authenticated-orcid":false,"given":"Eric A.","family":"Galburt","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis School of Medicine. 660 S. Euclid Ave., Box 8231. 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