{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:58:47Z","timestamp":1790791127332,"version":"4.1.0"},"reference-count":119,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["Investigator"],"award-info":[{"award-number":["Investigator"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The origin recognition complex (ORC) binds origins of replication and directs the loading of the Mcm2\u20137 replicative helicase at these sites. Five of the six ORC subunits are related to the AAA+ family of ATPases. Although functions for ATP hydrolysis by Cdc6 and the Mcm2\u20137 complex have been described, the essential role of ORC ATP hydrolysis remains unclear. We performed a genetic screen in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    for suppressors of the lethal phenotype of the\n                    <jats:italic>orc4-R267A<\/jats:italic>\n                    allele, which disrupts ORC ATP hydrolysis\n                    <jats:italic>in vitro<\/jats:italic>\n                    . We identified six causative mutations, five of which are distributed across different ORC subunits. The suppressor mutations in Orc1 and Orc4, but not those in other ORC subunits, increase the\n                    <jats:italic>in vitro<\/jats:italic>\n                    helicase loading activity of ATPase-defective ORC (ORC4R). Allele specificity studies show the alleles specifically suppress defects at ATPase interfaces within the ORC-Cdc6 complex. The sixth allele is a mutation in\n                    <jats:italic>TOA2<\/jats:italic>\n                    , a subunit of the TFIIA general transcription factor. Mutations in the general transcription factors TBP and TFIIB, and the large subunit of RNA Polymerase II also suppress\n                    <jats:italic>orc4-R267A<\/jats:italic>\n                    lethality, suggesting that reducing transcription is sufficient for suppression\n                    <jats:italic>.<\/jats:italic>\n                    Our study identifies multiple pathways to suppress the lethal phenotype of an ATPase-defective ORC allele and reveals a connection between ORC ATP hydrolysis and transcription.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0349465","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:34:49Z","timestamp":1790789689000},"page":"e0349465","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A lethal ORC ATPase mutation is suppressed by alterations in ORC and RNA Pol II transcription components"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5749-7998","authenticated-orcid":true,"given":"Luis E.","family":"Mart\u00ednez-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Massachusetts Institute of Technology","place":["Cambridge, MA, United States of America"],"department":["Department of Biology"]},{"name":"Howard Hughes Medical Institute","place":["Cambridge, MA, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2876-610X","authenticated-orcid":true,"given":"Stephen P.","family":"Bell","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology","place":["Cambridge, MA, United States of America"],"department":["Department of Biology"]},{"name":"Howard Hughes Medical Institute","place":["Cambridge, MA, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"3","key":"pone.0349465.ref001","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1534\/genetics.115.186452","article-title":"Chromosome duplication in Saccharomyces cerevisiae","volume":"203","author":"SP Bell","year":"2016","journal-title":"Genetics"},{"issue":"10","key":"pone.0349465.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/j.cub.2014.04.012","article-title":"DNA replication and oncogene-induced replicative stress","volume":"24","author":"SA Hills","year":"2014","journal-title":"Curr Biol"},{"issue":"6374","key":"pone.0349465.ref003","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/357128a0","article-title":"ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex","volume":"357","author":"SP 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