Yeast DNA polymerase η utilizes an induced-fit mechanism of nucleotide incorporation

M. Todd Washington, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

DNA polymerase η (Polη) is unique among eukaryotic DNA polymerases in its proficient ability to replicate through distorting DNA lesions, and Polη synthesizes DNA with a low fidelity. Here, we use pre-steady-state kinetics to investigate the mechanism of nucleotide incorporation by Polη and show that it utilizes an induced-fit mechanism to selectively incorporate the correct nucleotide. Polη discriminates poorly between the correct and incorrect nucleotide at both the initial nucleotide binding step and at the subsequent induced-fit conformational change step, which precedes the chemical step of phosphodiester bond formation. This property enables Polη to bypass lesions with distorted DNA geometries, and it bestows upon the enzyme a low fidelity.

Original languageEnglish (US)
Pages (from-to)917-927
Number of pages11
JournalCell
Volume107
Issue number7
DOIs
StatePublished - Dec 28 2001

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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