Lesion bypass activities of human DNA polymerase μ

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

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

DNA polymerase μ (Polμ) is a newly discovered member of the polymerase X family with unknown cellular function. The understanding of Polμ function should be facilitated by an understanding of its biochemical activities. By using purified human Polμ for biochemical analyses, we discovered the lesion bypass activities of this polymerase in response to several types of DNA damage. When it encountered a template 8-oxoguanine, abasic site, or 1,N6-ethenoadenine, purified human Polμ efficiently bypassed the lesion. Even bulky DNA adducts such as N-2-acetylaminofluorene-adducted guanine, (+)-and (-)-trans-anti-benzo[a]pyrene-N2-dG were unable to block the polymerase activity of human Polμ. Bypass of these simple base damage and bulky adducts was predominantly achieved by human Polμ through a deletion mechanism. The Polμ specificity of nucleotide incorporation indicates that the deletion resulted from primer realignment before translesion synthesis. Purified human Polμ also effectively bypassed a template cis-syn TT dimer. However, this bypass was achieved in a mainly error-free manner with AA incorporation opposite the TT dimer. These results provide new insights into the biochemistry of human Polμ and show that efficient translesion synthesis activity is not strictly confined to the Y family polymerases.

Original languageEnglish (US)
Pages (from-to)44582-44587
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number46
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Zhang, Y., Wu, X., Guo, D., Rechkoblit, O., Taylor, J. S., Geacintov, N. E., & Wang, Z. (2002). Lesion bypass activities of human DNA polymerase μ. Journal of Biological Chemistry, 277(46), 44582-44587. https://doi.org/10.1074/jbc.M207297200