MRC1-dependent scaling of the budding yeast DNA replication timing program

Genome Res. 2010 Jun;20(6):781-90. doi: 10.1101/gr.102764.109. Epub 2010 Mar 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cell Separation
  • DNA Replication Timing*
  • DNA, Fungal / biosynthesis*
  • Epistasis, Genetic
  • Flow Cytometry
  • Mutation
  • Reverse Transcriptase Polymerase Chain Reaction
  • S Phase
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • DNA, Fungal
  • MRC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins

Associated data

  • GEO/GSE17120