MRC1-dependent scaling of the budding yeast DNA replication timing program
Abstract
We describe the DNA replication timing programs of 14 yeast mutants with an extended S phase identified by a novel genome-wide screen. These mutants are associated with the DNA replication machinery, cell-cycle control, and dNTP synthesis and affect different parts of S phase. In 13 of the mutants, origin activation time scales with the duration of S phase. A limited number of origins become inactive in these strains, with inactive origins characterized by small replicons and distributed throughout S phase. In sharp contrast, cells deleted of MRC1, a gene implicated in replication fork stabilization and in the replication checkpoint pathway, maintained wild-type firing times despite over twofold lengthening of S phase. Numerous dormant origins were activated in this mutant. Our data suggest that most perturbations that lengthen S phase affect the entire program of replication timing, rather than a specific subset of origins, maintaining the relative order of origin firing time and delaying firing with relative proportions. Mrc1 emerges as a regulator of this robustness of the replication program.
Footnotes
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↵2 Corresponding author.
E-mail naama.barkai{at}weizmann.ac.il; fax 972-8-934-4108.
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[Supplemental material is available online at http://www.genome.org. The microarray data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE17120.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.102764.109.
- Received November 2, 2009.
- Accepted March 3, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
