RAD23 PHOSPHORYLATION IN DNA REPAIR AND PROTEASOME INTER

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We have been studying the mechanism of substrate recognition by the ubiquitin/proteasome pathway. We previously identified the yeast G-alpha protein as a target of the N-end rule pathway; a specific substrate-targeting mechanism of the ubiquitin system. G-alpha is a regulator of the mating response to yeast, and is functionally similar to its mammalian counterparts. We recently published a paper describing the isolation and detailed characterization of a degradation signal to G-alpha. Overexpression of the N-end rule pathway causes growth arrest in yeast cells. We isolated Rad23 as a suppressor of this toxicity. Rad23 was previously identified as a factor that is required for nucleotide excision repair in yeast and humans. We have recently reported that both yeast and human Rad23 3 proteins can form stable interactions with catalytically active proteasomes. Current experiments are designed to determine the sequences and conditions that mediate Rad23/proteasome interaction. We are also investigating the significance of phosphorylation in rad23 function. These studies form a major new direction in our laboratory.