title: Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway.
abstract: RAD53 and MEC1 are essential genes required for the transcriptional and cell cycle responses to DNA damage and DNA replication blocks. We have examined the essential function of these genes and found that their lethality but not their checkpoint defects can be suppressed by increased expression of genes encoding ribonucleotide reductase. Analysis of viable null alleles revealed that Mec1 plays a greater role in response to inhibition of DNA synthesis than Rad53. The loss of survival in mec1 and rad53 null or point mutants in response to transient inhibition of DNA synthesis is not a result of inappropriate anaphase entry but primarily to an inability to complete chromosome replication. We propose that this checkpoint pathway plays an important role in the maintenance of DNA synthetic capabilities when DNA replication is stressed.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030 USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Desany
authors.forename: A A
authors.initials: AA
authors.lastname: Alcasabas
authors.forename: J B
authors.initials: JB
authors.lastname: Bachant
authors.forename: S J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics; D004271:DNA, Fungal / Q000096:biosynthesis; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D005800:Genes, Fungal; D006918:Hydroxyurea / Q000633:toxicity; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D017354:Point Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D012264:Ribonucleotide Reductases; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D006918:Hydroxyurea