UC San Diego

During transcriptional elongation, RNA Polymerase (Pol II) may become stalled at DNA lesions. One way to resolve this transcriptional arrest is through Transcription Coupled-Nucleotide Excision Repair (TC-NER). Cockayne Syndrome Group B protein (CSB) is the first protein to be recruited and binds the upstream of stalled Pol II, alters the surrounding chromatin environment and allows other repair factors to access the DNA lesion. Many mutations in CSB are associated with Cockayne Syndrome (CS). Chapter 1 investigates the biochemical properties of CSB mutations observed in CS patients using Rhp26, the Schizosaccharomyces pombe ortholog of CSB. All six mutations studied show a decrease in chromatin remodelling and DNA translocation activities, both of which are important activities for CSB to execute its molecular function. In Chapter 2, we studied the regulation of CSB/Pol II interactions by its flanking regions using Rad26, the Saccharomyces cerevisiae ortholog of CSB. A conserved C-terminal region coupling motif promotes Rad26/Pol II interactions. Taken together, these results demonstrate that mutations to CSB that can be detrimental to its enzymatic activity and its role in maintaining genomic fidelity.