Fidelity of Human DNA Polymerase η*

By Robert E. Johnson, M. Washington, S. Prakash, L. Prakash. Journal of Biological Chemistry, 2000

395 citations recorded by the source corpus.

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 thehRAD30A gene, which encodes the DNA polymerase in humans, hPolη. Of the eukaryotic DNA polymerases, only human Polη and its yeast counterpart have the ability to replicate DNA containing acis-syn thymine-thymine (T-T) dimer. Here we measure the fidelity of hPolη on all four nondamaged template bases and at each thymine residue of a cis-syn T-T dimer. Opposite all four nondamaged template bases, hPolη misincorporates nucleotides with a frequency of ∼10−2-10−3, and importantly, hPolη synthesizes DNA opposite the T-T dimer with the same accuracy and efficiency as opposite the nondamaged DNA. The low fidelity of hPolη 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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f07688985696206ed8589df005022b3a2154e5bc

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In Genetics

1. S. Prakash
2. L. Prakash
3. Robert E. Johnson
4. B. Kaina
5. W. Roos

In Molecular Biology

1. S. Prakash
2. L. Prakash
3. Robert E. Johnson
4. L. Haracska
5. B. Kaina
6. W. Roos
7. M. Tomicic
8. M. Christmann

Citations in the corpus

• Role of DNA Polymerase η in the Bypass of a (6-4) TT Photoproduct (2001, methodology): “Both yeast and human Polh efficiently insert two A’s opposite the two T’s of the dimer and extend from the resulting primer (15, 27).”
• Mechanisms of human DNA repair: an update. (2003, background): “The human polymerase kappa (Pol␬; DINB; Gerlach et al., 1999, 2001; Johnson et al., 2000a; Ogi et al., 1999) is the homologue of the E. coli dinB-encoded DNA polymerase IV.”