Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp.
Bacteria employ a coordinated SOS response to DNA damage by enhancing transcription, translesion synthesis, and recombination; a similar phenomenon has not been reported in eukaryotes. Here, we demonstrate that the ubiquitination complex Rad6-Rad18 is required for the increased transcription of a large number of yeast genes in response to DNA damage. Rad6-Rad18 promotes DNA-damage-dependent transcriptional induction as well as checkpoint functions by catalyzing monoubiquitination at the K197 residue of the Rad17 subunit of the 9-1-1 complex. Rad17 ubiquitination invokes both DNA damage responsive pathways by promoting efficient Rad53 phosphorylation, possibly through the recruitment or maintenance of the 9-1-1 clamp at sites of lesions. Taken together, the Rad6-Rad18 complex is involved in the control of global gene regulation in a way reminiscent of the bacterial SOS response and plays key roles in coordinating several DNA damage response pathways through ubiquitination of two DNA clamps, PCNA and 9-1-1.
Fu
Yu
Y
Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada.
Zhu
Yu
Y
Zhang
Ke
K
Yeung
Mantek
M
Durocher
Daniel
D
Xiao
Wei
W
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D009687:Nuclear Proteins / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013014:SOS Response, Genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D054875:Ubiquitination
D018797:Cell Cycle Proteins; C108125:DDI1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; C501395:RAD17 protein, S cerevisiae; C063607:RAD18 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D045647:DNA Glycosylases; C445668:MAG1 protein, S cerevisiae