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Fidelity of human DNA polymerase eta
Journal article   Open access   Peer reviewed

Fidelity of human DNA polymerase eta

Robert E Johnson, M Todd Washington, Satya Prakash and Louise Prakash
The Journal of biological chemistry, Vol.275(11), pp.7447-7450
03/17/2000
DOI: 10.1074/jbc.275.11.7447
PMID: 10713043
url
https://doi.org/10.1074/jbc.275.11.7447View
Published (Version of record) Open Access

Abstract

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(eta). Of the eukaryotic DNA polymerases, only human Pol(eta) 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(eta) on all four nondamaged template bases and at each thymine residue of a cis-syn T-T dimer. Opposite all four nondamaged template bases, hPol(eta) misincorporates nucleotides with a frequency of approximately 10(-2)-10(-3), and importantly, hPol(eta) synthesizes DNA opposite the T-T dimer with the same accuracy and efficiency as opposite the nondamaged DNA. The low fidelity of hPol(eta) 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.
 DNA Replication Mutation Recombinant Proteins - metabolism Xeroderma Pigmentosum - genetics Deoxyribonucleotides - metabolism Humans Thymidine DNA Damage DNA-Directed DNA Polymerase - metabolism Pyrimidine Dimers DNA-Directed DNA Polymerase - genetics

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