Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast.
Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork stalled at the lesion site, the replication checkpoint presumably coordinates the action of lesion bypass processes with the replisome. However, it has remained unclear as to which of the lesion bypass processes-translesion synthesis (TLS) and/or template switching-depend on the activation of the replication checkpoint. Here we determine if the Mec1 kinase and the subunits of the checkpoint clamp and the clamp loader are required for TLS. We show that proficient TLS can occur in the absence of these checkpoint proteins in nucleotide excision repair (NER)-proficient cells; however, in the absence of NER, checkpoint protein-mediated Rev1 phosphorylation contributes to increasing the proficiency of DNA polymerase zeta-dependent TLS.
Pagès
Vincent
V
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
Santa Maria
Sergio R
SR
Prakash
Louise
L
Prakash
Satya
S
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D016296:Mutagenesis / Q000528:radiation effects; D009713:Nucleotidyltransferases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004269:DNA, Bacterial; D047908:Intracellular Signaling Peptides and Proteins; D009713:Nucleotidyltransferases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; C440014:LCD1 protein, S cerevisiae; C088937:MEC1 protein, S cerevisiae; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases