Fidelity of Human DNA Polymerase η

Robert E. Johnson, M. Todd Washington, Satya Prakash, Louise Prakash
2000 Journal of Biological Chemistry  
Xeroderma pigmentosum (XP) patients are highly sensitive to sunlight, and they suffer from a high incidence of skin cancers. The variant form of XP results from mutations in the hRAD30A gene, which encodes the DNA polymerase in humans, hPol. Of the eukaryotic DNA polymerases, only human Pol and its yeast counterpart have the ability to replicate DNA containing a cis-syn thymine-thymine (T-T) dimer. Here we measure the fidelity of hPol on all four nondamaged template bases and at each thymine
more » ... idue of a cis-syn T-T dimer. Opposite all four nondamaged template bases, hPol misincorporates nucleotides with a frequency of ϳ10 ؊2 -10 ؊3 , and importantly, hPol synthesizes DNA opposite the T-T dimer with the same accuracy and efficiency as opposite the nondamaged DNA. The low fidelity of hPol may derive from a flexible active site that renders the enzyme more tolerant of geometric distortions in DNA and enables it to synthesize DNA past a T-T dimer.
doi:10.1074/jbc.275.11.7447 pmid:10713043 fatcat:zwoby2rwsjg5damiawrkwmmmgq