Yeast Rap1 contributes to genomic integrity by activating DNA damage repair genes.
Rap1 (repressor-activator protein 1) is a multifunctional protein that controls telomere function, silencing and the activation of glycolytic and ribosomal protein genes. We have identified a novel function for Rap1, regulating the ribonucleotide reductase (RNR) genes that are required for DNA repair and telomere expansion. Both the C terminus and DNA-binding domain of Rap1 are required for the activation of the RNR genes, and the phenotypes of different Rap1 mutants suggest that it utilizes both regions to carry out distinct steps in the activation process. Recruitment of Rap1 to the RNR3 gene is dependent on activation of the DNA damage checkpoint and chromatin remodelling by SWI/SNF. The dependence on SWI/SNF for binding suggests that Rap1 acts after remodelling to prevent the repositioning of nucleosomes back to the repressed state. Furthermore, the recruitment of Rap1 requires TAF(II)s, suggesting a role for TFIID in stabilizing activator binding in vivo. We propose that Rap1 acts as a rheostat controlling nucleotide pools in response to shortened telomeres and DNA damage, providing a mechanism for fine-tuning the RNR genes during checkpoint activation.
Tomar
Raghuvir S
RS
Department of Biochemistry and Molecular Biology, Center for Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
Zheng
Suting
S
Brunke-Reese
Deborah
D
Wolcott
Holly N
HN
Reese
Joseph C
JC
D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D009154:Mutation; D011401:Promoter Regions, Genetic; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D000089804:Shelterin Complex; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C440829:RAP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; C517042:RNR3 protein, S cerevisiae; D012262:Ribonucleoside Diphosphate Reductase