Mrc1 is required for normal progression of replication forks throughout chromatin in S. cerevisiae.
Mrc1 associates with replication forks, where it transmits replication stress signals and is required for normal replisome pausing in response to nucleotide depletion. Mrc1 also plays a poorly understood role in DNA replication, which appears distinct from its role in checkpoint signaling. Here, we demonstrate that Mrc1 functions constitutively to promote normal replication fork progression. In mrc1Delta cells, replication forks proceed slowly throughout chromatin, rather than being specifically defective in pausing and progression through loci that impede fork progression. Analysis of genetic interactions with Rrm3, a DNA helicase required to resolve paused forks, indicates that Mrc1 checkpoint signaling is dispensable for the resolution of stalled replication forks and suggests that replication forks lacking Mrc1 create DNA damage that must be repaired by Rrm3. These findings elucidate a central role for Mrc1 in normal replisome function, which is distinct from its role as a checkpoint mediator, but nevertheless critical to genome stability.
Szyjka
Shawn J
SJ
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
Viggiani
Christopher J
CJ
Aparicio
Oscar M
OM
D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002843:Chromatin / Q000502:physiology*; D004265:DNA Helicases / Q000502:physiology; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D009154:Mutation; D009687:Nuclear Proteins / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*
C102209:CDC45 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C441579:MRC1 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C459081:Rrm3 protein, S cerevisiae; D004265:DNA Helicases