Checkpoint proteins control morphogenetic events during DNA replication stress in Saccharomyces cerevisiae.
In response to DNA replication stress in Saccharomyces cerevisiae, the DNA replication checkpoint maintains replication fork stability, prevents precocious chromosome segregation, and causes cells to arrest as large-budded cells. The checkpoint kinases Mec1 and Rad53 act in this checkpoint. Treatment of mec1 or rad53Delta mutants with replication inhibitors results in replication fork collapse and inappropriate partitioning of partially replicated chromosomes, leading to cell death. We describe a previously unappreciated function of various replication stress checkpoint proteins, including Rad53, in the control of cell morphology. Checkpoint mutants have aberrant cell morphology and cell walls, and show defective bud site selection. Rad53 shows genetic interactions with septin ring pathway components, and, along with other checkpoint proteins, controls the timely degradation of Swe1 during replication stress, thereby facilitating proper bud growth. Thus, checkpoint proteins play an important role in coordinating morphogenetic events with DNA replication during replication stress.
Enserink
Jorrit M
JM
Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Smolka
Marcus B
MB
Zhou
Huilin
H
Kolodner
Richard D
RD
D000199:Actins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D064447:Checkpoint Kinase 2; D048749:Cytokinesis; D004261:DNA Replication; D009024:Morphogenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D000199:Actins; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; C099685:SWE1 protein, S cerevisiae; D064447:Checkpoint Kinase 2; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae