{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T12:02:47Z","timestamp":1774958567850,"version":"3.50.1"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>The Lyme disease spirochete <jats:italic>Borrelia burgdorferi<\/jats:italic>, encodes an elaborate antigenic variation system that promotes the ongoing variation of a major surface lipoprotein, VlsE. Changes in VlsE are continual and always one step ahead of the host acquired immune system, which requires 1\u20132 weeks to generate specific antibodies. By the time this happens, new VlsE variants have arisen that escape immunosurveillance, providing an avenue for persistent infection. This antigenic variation system is driven by segmental gene conversion events that transfer information from a series of silent cassettes (<jats:italic>vls2-16)<\/jats:italic> to the expression locus, <jats:italic>vlsE.<\/jats:italic> The molecular details of this process remain elusive. Recombinational switching at <jats:italic>vlsE<\/jats:italic> is RecA-independent and the only required factor identified to date is the RuvAB branch migrase. In this work we have used next generation long-read sequencing to analyze the effect of several DNA replication\/recombination\/repair gene disruptions on the frequency of gene conversions at <jats:italic>vlsE<\/jats:italic> and report a requirement for the mismatch repair protein MutL. Site directed mutagenesis of <jats:italic>mutL<\/jats:italic> suggests that the putative MutL endonuclease activity is required for recombinational switching at <jats:italic>vlsE.<\/jats:italic> This is the first report of an unexpected essential role for MutL in a bacterial recombination system and expands the known function of this protein as well as our knowledge of the details of the novel recombinational switching mechanism for <jats:italic>vlsE<\/jats:italic> variation.<\/jats:p>","DOI":"10.3389\/fmicb.2022.888494","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T01:57:11Z","timestamp":1652925431000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The Putative Endonuclease Activity of MutL Is Required for the Segmental Gene Conversion Events That Drive Antigenic Variation of the Lyme Disease Spirochete"],"prefix":"10.3389","volume":"13","author":[{"given":"Mildred","family":"Castellanos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore B.","family":"Verhey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeleine","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Chaconas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4831","DOI":"10.1093\/nar\/gkz115","article-title":"Binding of the regulatory domain of MutL to the sliding beta-clamp is species specific.","volume":"47","author":"Almawi","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1098\/rstb.2008.0202","article-title":"Activation-induced cytidine deaminase-mediated hypermutation in the DT40 cell line.","volume":"364","author":"Arakawa","year":"2009","journal-title":"Philos Trans R Soc Lond B Biol. 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