{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:43:56Z","timestamp":1790052236544,"version":"4.0.1"},"reference-count":77,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,10]],"date-time":"2012-12-10T00:00:00Z","timestamp":1355097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2013,1]]},"abstract":"Summary<\/jats:title>Binding of the O<\/jats:styled-content>rigin R<\/jats:styled-content>ecognition C<\/jats:styled-content>omplex (ORC<\/jats:styled-content>) to replication origins is essential for initiation of DNA<\/jats:styled-content> replication, but ORC<\/jats:styled-content> has non\u2010essential functions outside of DNA<\/jats:styled-content> replication, including in heterochromatic gene silencing and telomere maintenance. T<\/jats:styled-content>rypanosoma brucei,<\/jats:italic> a protozoan parasite that causes human A<\/jats:styled-content>frican trypanosomiasis, uses antigenic variation as a major virulence mechanism to evade the host's immune attack by expressing its major surface antigen, the V<\/jats:styled-content>ariant S<\/jats:styled-content>urface G<\/jats:styled-content>lycoprotein (VSG<\/jats:styled-content>), in a monoallelic manner. An Orc<\/jats:styled-content>1\/Cdc<\/jats:styled-content>6 homologue has been identified in T<\/jats:styled-content>.\u2009brucei,<\/jats:italic> but its role in DNA<\/jats:styled-content> replication has not been directly confirmed and its potential involvement in VSG<\/jats:styled-content><\/jats:italic> repression or switching has not been thoroughly investigated. In this study, we show that TbOrc<\/jats:styled-content>1 is essential for nuclear DNA<\/jats:styled-content> replication in mammalian\u2010infectious bloodstream and tsetse procyclic forms (BF<\/jats:styled-content> and PF<\/jats:styled-content>). Depletion of TbOrc<\/jats:styled-content>1 resulted in derepression of telomere\u2010linked silent VSG<\/jats:italic>s<\/jats:styled-content> in both BF<\/jats:styled-content> and PF<\/jats:styled-content>, and increased VSG<\/jats:styled-content><\/jats:italic> switching particularly through the in situ<\/jats:italic> transcriptional switching mechanism. TbOrc<\/jats:styled-content>1 associates with telomere repeats but appears to do so independently of two known T<\/jats:styled-content>.\u2009brucei<\/jats:italic> telomere proteins, TbRAP<\/jats:styled-content>1 and TbTRF<\/jats:styled-content>. We conclude that TbOrc<\/jats:styled-content>1 has conserved functions in DNA<\/jats:styled-content> replication and is also required to control telomere\u2010linked VSG<\/jats:styled-content><\/jats:italic> expression and VSG<\/jats:styled-content><\/jats:italic> switching.<\/jats:p>","DOI":"10.1111\/mmi.12093","type":"journal-article","created":{"date-parts":[[2012,12,10]],"date-time":"2012-12-10T10:30:21Z","timestamp":1355135421000},"page":"196-210","source":"Crossref","is-referenced-by-count":64,"title":["T<\/scp>rypanosoma brucei<\/i>Orc<\/scp>1 is essential for nuclear DNA<\/scp> replication and affects both VSG<\/scp><\/i> silencing and VSG<\/scp><\/i> switching"],"prefix":"10.1111","volume":"87","author":[{"given":"Imaan","family":"Benmerzouga","sequence":"first","affiliation":[{"name":"Center for Gene Regulation in Health & Disease Department of Biological, Geological, and Environmental Sciences Cleveland State University 2121 Euclid Avenue Cleveland OH 44115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeniffer","family":"Concepci\u00f3n\u2010Acevedo","sequence":"additional","affiliation":[{"name":"Department of Microbiology University of Massachusetts 639 North Pleasant Street Amherst MA 01003 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee\u2010Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Parasitology The Rockefeller University 1230 York Avenue New York NY 10065 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthula V.","family":"Vandoros","sequence":"additional","affiliation":[{"name":"Department of Microbiology University of Massachusetts 639 North Pleasant Street Amherst MA 01003 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A. 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