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.
Mesh Terms:
Cell Cycle, Cell Cycle Proteins, DNA Damage, DNA Glycosylases, DNA-Binding Proteins, Gene Expression Regulation, Fungal, Nuclear Proteins, Proliferating Cell Nuclear Antigen, SOS Response (Genetics), Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic, Ubiquitin-Conjugating Enzymes, Ubiquitination
Cell Cycle, Cell Cycle Proteins, DNA Damage, DNA Glycosylases, DNA-Binding Proteins, Gene Expression Regulation, Fungal, Nuclear Proteins, Proliferating Cell Nuclear Antigen, SOS Response (Genetics), Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic, Ubiquitin-Conjugating Enzymes, Ubiquitination
Cell
Date: May. 16, 2008
PubMed ID: 18485869
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