TY - JOUR A1 - Koren, Amnon A1 - Soifer, Ilya A1 - Barkai, Naama T1 - MRC1-dependent scaling of the budding yeast DNA replication timing program Y1 - 2010/06/01 JF - Genome Research JO - Genome Research SP - 781 EP - 790 DO - 10.1101/gr.102764.109 VL - 20 IS - 6 UR - http://genome.cshlp.org/content/20/6/781.abstract N2 - 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. ER -