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Accuracy of lesion bypass by yeast and human DNA polymerase η
Journal article   Open access   Peer reviewed

Accuracy of lesion bypass by yeast and human DNA polymerase η

M. Todd Washington, Robert E Johnson, Louise Prakash and Satya Prakash
Proceedings of the National Academy of Sciences - PNAS, Vol.98(15), pp.8355-8360
Colloquium Paper
07/17/2001
DOI: 10.1073/pnas.121007298
PMCID: PMC37443
PMID: 11459975
url
https://doi.org/10.1073/pnas.121007298View
Published (Version of record) Open Access

Abstract

DNA polymerase η (Polη) functions in the error-free bypass of UV-induced DNA lesions, and a defect in Polη in humans causes the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Both yeast and human Polη replicate through a cis-syn thymine-thymine dimer (TT dimer) by inserting two As opposite the two Ts of the dimer. Polη, however, is a low-fidelity enzyme, and it misinserts nucleotides with a frequency of ≈ 10 −2 to 10 −3 opposite the two Ts of the TT dimer as well as opposite the undamaged template bases. This low fidelity of nucleotide insertion seems to conflict with the role of Polη in the error-free bypass of UV lesions. To resolve this issue, we have examined the ability of human and yeast Polη to extend from paired and mispaired primer termini opposite a TT dimer by using steady-state kinetic assays. We find that Polη extends from mispaired primer termini on damaged and undamaged DNAs with a frequency of ≈ 10 −2 to 10 −3 relative to paired primer termini. Thus, after the incorporation of an incorrect nucleotide, Polη would dissociate from the DNA rather than extend from the mispair. The resulting primer-terminal mispair then could be subject to proofreading by a 3′→5′ exonuclease. Replication through a TT dimer by Polη then would be more accurate than that predicted from the fidelity of nucleotide incorporation alone.
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