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Reference: Fu Y, et al. (2008) Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp. Cell 133(4):601-11

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Abstract

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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Fu Y, Zhu Y, Zhang K, Yeung M, Durocher D, Xiao W
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