by Peng Xu
A number of factors, including oxidative stress, damage DNA and cause challenges during DNA replication. The most common oxidative “lesion” – 8-oxoG – is associated with cancer, aging, hepatitis and infertility. Among various mechanisms cells have for removing or bypassing lesions, Y-family polymerases bypass sites of damaged DNA in a less error-prone fashion.
In a “Paper of the Week” published online April 23 by the Journal of Biological Chemistry, Martin Egli, Ph.D., and colleagues used kinetic and mass-spectrometric studies to demonstrate that a member of the Y-polymerase family, human polymerase eta (hPol-eta), bypasses 8-oxoG in a largely error-free manner by preferentially incorporating dCTP (one of the DNA building blocks) opposite 8-oxoG.
Crystal structures of the native hPol-eta complex demonstrate that an arginine amino acid in the enzyme’s finger domain prevents formation of the more error-prone 8-oxoG:A pair. These novel findings provide a complete kinetic and structural framework for understanding how hPol-eta accurately bypasses the most common oxidative DNA lesion.
This research was supported by National Institutes of Health grants ES010375, CA160032 and ES000267.
Send suggestions for articles to highlight in Aliquots and any other feedback about the column to aliquots@vanderbilt.edu
