Mcm2 phosphorylation and the response to replicative stress.

BMC Genetics
Brent E SteadMegan J Davey

Abstract

The replicative helicase in eukaryotic cells is comprised of minichromosome maintenance (Mcm) proteins 2 through 7 (Mcm2-7) and is a key target for regulation of cell proliferation. In addition, it is regulated in response to replicative stress. One of the protein kinases that targets Mcm2-7 is the Dbf4-dependent kinase Cdc7 (DDK). In a previous study, we showed that alanine mutations of the DDK phosphorylation sites at S164 and S170 in Saccharomyces cerevisiae Mcm2 result in sensitivity to caffeine and methyl methanesulfonate (MMS) leading us to suggest that DDK phosphorylation of Mcm2 is required in response to replicative stress. We show here that a strain with the mcm2 allele lacking DDK phosphorylation sites (mcm2AA) is also sensitive to the ribonucleotide reductase inhibitor, hydroxyurea (HU) and to the base analogue 5-fluorouracil (5-FU) but not the radiomimetic drug, phleomycin. We screened the budding yeast non-essential deletion collection for synthetic lethal interactions with mcm2AA and isolated deletions that include genes involved in the control of genome integrity and oxidative stress. In addition, the spontaneous mutation rate, as measured by mutations in CAN1, was increased in the mcm2AA strain compared to wild...Continue Reading

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Citations

Aug 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Irina Bruck, Daniel L Kaplan
Apr 2, 2014·Seminars in Cell & Developmental Biology·Juergen Zech, Jacob Zeuthen Dalgaard
Jul 29, 2015·PLoS Genetics·Pamela Y SandovalGeoffrey M Kapler
Nov 9, 2014·Genetics·Lorraine S SymingtonMichael Lisby
Apr 4, 2013·The Journal of Biological Chemistry·Matthew D RamerBernard P Duncker
Dec 5, 2014·The Journal of Biological Chemistry·Irina Bruck, Daniel L Kaplan
Aug 1, 2018·Cell & Bioscience·Liangru Fei, Hongtao Xu

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Methods Mentioned

BETA
dissection
protein folding
protein-folding

Software Mentioned

ImageQuant
Cytoscape
SGD

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