The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor.
We have identified the yeast CRT1 gene as an effector of the DNA damage and replication checkpoint pathway. CRT1 encodes a DNA-binding protein that recruits the general repressors Ssn6 and Tup1 to the promoters of damage-inducible genes. Derepression of the Crt1 regulon suppresses the lethality of mec1 and rad53 null alleles and is essential for cell viability during replicative stress. In response to DNA damage and replication blocks, Crt1 becomes hyperphosphorylated and no longer binds DNA, resulting in transcriptional induction. CRT1 is autoregulated and is itself induced by DNA damage, indicating the existence of a negative feedback pathway that facilitates return to the repressed state after elimination of damage. The inhibition of an autoregulatory repressor in response to DNA damage is a strategy conserved throughout prokaryotic and eukaryotic evolution.
Huang
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M
Howard Hughes Medical Institute, Verna & Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA.
Zhou
Z
Z
Elledge
S J
SJ
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005805:Genes, MHC Class I / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D000071701:Regulatory Factor X Transcription Factors; D018085:Regulon / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012264:Ribonucleotide Reductases / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*
C065455:CYC8 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C114542:RFX1 protein, S cerevisiae; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; D014157:Transcription Factors; D012264:Ribonucleotide Reductases; D011494:Protein Kinases; C104169:DUN1 protein, S cerevisiae; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae