{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:15:13Z","timestamp":1791400513160,"version":"4.3.3"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,8,31]],"date-time":"2015-08-31T00:00:00Z","timestamp":1440979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AI 084734"],"award-info":[{"award-number":["AI 084734"]}]},{"name":"AI","award":["048417"],"award-info":[{"award-number":["048417"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The regulators of <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic><\/jats:styled-content><jats:italic>ycobacterium tuberculosis<\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> replication are largely unknown. Here, we demonstrate that in synchronously replicating <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic><\/jats:styled-content><jats:italic>. tuberculosis<\/jats:italic>, <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content> access to origin of replication (<jats:italic>ori<\/jats:italic><jats:italic><jats:styled-content style=\"fixed-case\">C<\/jats:styled-content><\/jats:italic>) is enriched in the post\u2010replication (<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>) period. The increased <jats:italic>ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content> binding results from elevated <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content> phosphorylation (<jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content>\u223c<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>) as evidenced by reduced expression of <jats:italic>dna<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>N<\/jats:italic><\/jats:styled-content>, <jats:italic>dna<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>A<\/jats:italic><\/jats:styled-content> and increased expression of select cell division targets. Overproduction of gain\u2010of\u2010function <jats:styled-content style=\"fixed-case\">MtrA<jats:sub>Y102C<\/jats:sub><\/jats:styled-content> advanced the <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content>\u2005<jats:italic>ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content> access to the <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> period, reduced <jats:italic>dna<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>A<\/jats:italic><\/jats:styled-content> and <jats:italic>dna<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>N<\/jats:italic><\/jats:styled-content> expression, interfered with replication synchrony and compromised cell division. Overproduction of wild\u2010type (<jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content>+) or phosphorylation\u2010defective <jats:styled-content style=\"fixed-case\">MtrA<jats:sub>D56N<\/jats:sub><\/jats:styled-content> did not promote <jats:italic>ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content> access in the <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> period, nor affected cell cycle progression. <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content> interacts with <jats:styled-content style=\"fixed-case\">DnaA<\/jats:styled-content> signaling a possibility that <jats:styled-content style=\"fixed-case\">DnaA<\/jats:styled-content> helps load <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content> on <jats:italic>ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content>. Therefore, <jats:italic>ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content> sequestration by <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content>\u223c<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> in the <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> period may normally serve to prevent untimely initiations and that <jats:styled-content style=\"fixed-case\">DnaA<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content> interactions may facilitate regulated <jats:italic>ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content> replication. Finally, despite the near sequence identity of <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic><\/jats:styled-content><jats:italic>. smegmatis<\/jats:italic> and <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic><\/jats:styled-content><jats:italic>. tuberculosis<\/jats:italic>, the <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic><\/jats:styled-content><jats:italic>. smegmatis ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content> is not <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content>\u2010target. We conclude that <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic><\/jats:styled-content><jats:italic>. tuberculosis ori<\/jats:italic><jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><\/jats:styled-content> has evolved to be regulated by <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content> and that cell cycle progression in this organisms are governed, at least in part, by oscillations in the <jats:styled-content style=\"fixed-case\">MtrA<\/jats:styled-content>\u223c<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> levels.<\/jats:p>","DOI":"10.1111\/mmi.13144","type":"journal-article","created":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T10:26:47Z","timestamp":1437733607000},"page":"586-604","source":"Crossref","is-referenced-by-count":41,"title":["<scp><i>M<\/i><\/scp><i>ycobacterium tuberculosis ori<\/i><scp>C<\/scp> sequestration by <scp>MtrA<\/scp> response regulator"],"prefix":"10.1111","volume":"98","author":[{"given":"Gorla","family":"Purushotham","sequence":"first","affiliation":[{"name":"Biomedical Research The University of Health Science Center at Tyler  Tyler TX 75708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna B.","family":"Sarva","sequence":"additional","affiliation":[{"name":"Biomedical Research The University of Health Science Center at Tyler  Tyler TX 75708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Blaszczyk","sequence":"additional","affiliation":[{"name":"Biomedical Research The University of Health Science Center at Tyler  Tyler TX 75708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malini","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Biomedical Research The University of Health Science Center at Tyler  Tyler TX 75708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murty V.","family":"Madiraju","sequence":"additional","affiliation":[{"name":"Biomedical Research The University of Health Science Center at Tyler  Tyler TX 75708 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2011.01.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601266"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05333.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/31159"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(68)90425-7"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1998.tb13040.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80502-4"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12866"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni013"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05137.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi602546q"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12337"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks990"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1915"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04459.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2006.08.005"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.7.2233-2243.2005"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2314"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06109.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1561207"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004139"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008629200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-10-242"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1128\/JB.181.7.2252-2256.1999","article-title":"Oxygen depletion\u2010induced dormancy in Mycobacterium bovis BCG","volume":"181","author":"Lim A.","year":"1999","journal-title":"J Bacteriol"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05068.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.044"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06523.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07110.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506914103"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.346544"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01005-12"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.179.20.6311-6317.1997"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00148-1"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80995-2"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.120"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.040097"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03765.x"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02617.x"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.25832-0"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3470"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012922"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.16.3.463-496.2003"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.357715"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02125-14"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06825.x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.17.3.528-530.1977"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3630305"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.13.3832-3838.2000"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040338"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05853.x"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fmmi.13144","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.13144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T14:44:42Z","timestamp":1696171482000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mmi.13144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,31]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1111\/mmi.13144"],"URL":"https:\/\/doi.org\/10.1111\/mmi.13144","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,31]]}}}