|Institution:||University of North Carolina – Chapel Hill|
|Full text PDF:||http://dc.lib.unc.edu/u?/etd,1351|
The trans-syn cyclobutane pyrimidine dimer is a minor, but biologically significant ultraviolet photoproduct that is produced primarily in single-strand DNA. The only known repair system for this lesion is nucleotide excision repair. In this study I investigated the recognition and repair of the trans-syn cyclobutane thymine dimer by mammalian excision nuclease. I find that the trans-syn cyclobutane thymine dimer is recognized by RPA, XPA, and XPC damage sensor proteins with high specificity comparable to that of the [6-4] photoproduct; however, this lesion is excised by the mammalian excision nuclease with efficiency comparable to that of the poorly recognized cis-syn cyclobutane pyrimidine dimer. These data suggest that kinetic factors, after the initial damage recognition step, play a major role in the overall catalytic proficiency of the mammalian excision nuclease.