Error-prone lesion bypass by human DNA polymerase η

Yanbin Zhang, Fenghua Yuan, Xiaohua Wu, Olga Rechkoblit, John Stephen Taylor, Nicholas E. Geacintov, Zhigang Wang

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

DNA lesion bypass is an important cellular response to genomic damage during replication. Human DNA polymerase η (Polη), encoded by the Xeroderma pigmentosum variant (XPV) gene, is known for its activity of error-free translesion synthesis opposite a TT cis-syn cyclobutane dimer. Using purified human Polη, we have examined bypass activities of this polymerase opposite several other DNA lesions. Human Polη efficiently bypassed a template 8-oxoguanine, incorporating an A or a C opposite the lesion with similar efficiencies. Human Polη effectively bypassed a template abasic site, incorporating an A and less frequently a G opposite the lesion. Significant -1 deletion was also observed when the template base 5' to the abasic site is a T. Human Polη partially bypassed a template (+)-trans-anti-benzo[a]pyrene-N2-dG and predominantly incorporated an A, less frequently a T, and least frequently a G or a C opposite the lesion. This specificity of nucleotide incorporation correlates well with the known mutation spectrum of (+)-trans-anti-benzo [a]pyrene-N2-dG lesion in mammalian cells. These results show that human Polη is capable of error-prone translesion DNA syntheses in vitro and suggest that Polη may bypass certain lesions with a mutagenic consequence in humans.

Original languageEnglish (US)
Pages (from-to)4717-4724
Number of pages8
JournalNucleic acids research
Volume28
Issue number23
StatePublished - Dec 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Zhang, Y., Yuan, F., Wu, X., Rechkoblit, O., Taylor, J. S., Geacintov, N. E., & Wang, Z. (2000). Error-prone lesion bypass by human DNA polymerase η. Nucleic acids research, 28(23), 4717-4724.