Two subunits of human ORC are dispensable for DNA replication and proliferation

The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal o...

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Autores principales: Shibata, Etsuko, Kiran, Manjari, Shibata, Yoshiyuki, Singh, Samarendra, Kiran, Shashi, Dutta, Anindya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Cell Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5245961/
https://www.ncbi.nlm.nih.gov/pubmed/27906128
http://dx.doi.org/10.7554/eLife.19084
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author Shibata, Etsuko
Kiran, Manjari
Shibata, Yoshiyuki
Singh, Samarendra
Kiran, Shashi
Dutta, Anindya
author_facet Shibata, Etsuko
Kiran, Manjari
Shibata, Yoshiyuki
Singh, Samarendra
Kiran, Shashi
Dutta, Anindya
author_sort Shibata, Etsuko
collection PubMed
description The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. The ORC1 or ORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication. Thus, either the ORC ring lacking a subunit, even its ATPase subunit, can load enough MCM2-7 in partnership with CDC6 to initiate DNA replication, or cells have an ORC-independent, CDC6-dependent mechanism to load MCM2-7 on origins of replication DOI: http://dx.doi.org/10.7554/eLife.19084.001
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spelling pubmed-52459612017-01-25 Two subunits of human ORC are dispensable for DNA replication and proliferation Shibata, Etsuko Kiran, Manjari Shibata, Yoshiyuki Singh, Samarendra Kiran, Shashi Dutta, Anindya eLife Cell Biology The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. The ORC1 or ORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication. Thus, either the ORC ring lacking a subunit, even its ATPase subunit, can load enough MCM2-7 in partnership with CDC6 to initiate DNA replication, or cells have an ORC-independent, CDC6-dependent mechanism to load MCM2-7 on origins of replication DOI: http://dx.doi.org/10.7554/eLife.19084.001 eLife Sciences Publications, Ltd 2016-12-01 /pmc/articles/PMC5245961/ /pubmed/27906128 http://dx.doi.org/10.7554/eLife.19084 Text en © 2016, Shibata et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Shibata, Etsuko
Kiran, Manjari
Shibata, Yoshiyuki
Singh, Samarendra
Kiran, Shashi
Dutta, Anindya
Two subunits of human ORC are dispensable for DNA replication and proliferation
title Two subunits of human ORC are dispensable for DNA replication and proliferation
title_full Two subunits of human ORC are dispensable for DNA replication and proliferation
title_fullStr Two subunits of human ORC are dispensable for DNA replication and proliferation
title_full_unstemmed Two subunits of human ORC are dispensable for DNA replication and proliferation
title_short Two subunits of human ORC are dispensable for DNA replication and proliferation
title_sort two subunits of human orc are dispensable for dna replication and proliferation
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5245961/
https://www.ncbi.nlm.nih.gov/pubmed/27906128
http://dx.doi.org/10.7554/eLife.19084
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