Two subunits of human ORC are dispensable for DNA replication and proliferation
- University of Virginia School of Medicine, United States
Abstract
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
Data availability
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Data from: ORC is dispensable for DNA replication initiation, but essential for repression of Rb- and polycomb-regulated genesAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
National Institutes of Health (CA060499)
- Anindya Dutta
National Institutes of Health (CA166054)
- Anindya Dutta
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kevin Struhl, Harvard Medical School, United States
Version history
- Received: June 23, 2016
- Accepted: December 1, 2016
- Accepted Manuscript published: December 1, 2016 (version 1)
- Version of Record published: January 19, 2017 (version 2)
Copyright
© 2016, Shibata et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Two subunits of human ORC are dispensable for DNA replication and proliferation
eLife 5:e19084.
https://doi.org/10.7554/eLife.19084
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