Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- And late-replicating euchromatin

Hoggard, Timothy, Müller, Carolin A., Nieduszynski, Conrad A. ORCID: https://orcid.org/0000-0003-2001-076X, Weinreich, Michael and Fox, Catherine A. (2020) Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early- And late-replicating euchromatin. Proceedings of the National Academy of Sciences of the United States of America, 117 (25). pp. 14314-14321. ISSN 0027-8424

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Abstract

A eukaryotic chromosome relies on the function of multiple spatially distributed DNA replication origins for its stable inheritance. The spatial location of an origin is determined by the chromosomal position of an MCM complex, the inactive form of the DNA replicative helicase that is assembled onto DNA in G1-phase (also known as origin licensing). While the biochemistry of origin licensing is understood, the mechanisms that promote an adequate spatial distribution ofMCM complexes across chromosomes are not. We have elucidated a role for the Sir2 histone deacetylase in establishing the normal distribution of MCM complexes across Saccharomyces cerevisiae chromosomes. In the absence of Sir2, MCM complexes accumulated within both early-replicating euchromatin and telomeric heterochromatin, and replication activity within these regions was enhanced. Concomitantly, the duplication of several regions of late-replicating euchromatin were delayed. Thus, Sir2- mediated attenuation of origin licensing within both euchromatin and telomeric heterochromatin established the normal spatial distribution of origins across yeast chromosomes important for normal genome duplication.

Item Type: Article
Additional Information: Funding Information: ACKNOWLEDGMENTS. We thank Melissa Harrison (University of Wisconsin– Madison) for critiquing early drafts of the manuscript, and Erika Shor (Center for Discovery and Innovation, Hakensack Meridian Health), Xiaolan Zhao (Memorial Sloan Kettering Cancer Center), and members of the C.A.F. laboratory for thoughtful discussions. Support for this work was provided by NIH GM056890 to C.A.F., Biotechnology and Biological Sciences Research Council Grant BB/N016858 to C.A.M. and C.A.N., and Wellcome Trust Investigator Award 110064/Z/15/Z to C.A.N. Publisher Copyright: © 2020 National Academy of Sciences. All rights reserved.
Uncontrolled Keywords: chromatin,chromosomes,origin licensing,sir,yeast,general ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 07 Sep 2022 14:30
Last Modified: 22 Sep 2022 18:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/87849
DOI: 10.1073/pnas.2004664117

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