Protein-Template-Directed Synthesis across an Acrolein-Derived DNA Adduct by Yeast Rev1 DNA Polymerase

Deepak T. Nair, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Acrolein is generated as the end product of lipid peroxidation and is also a ubiquitous environmental pollutant. Its reaction with the N2 of guanine leads to a cyclic γ-HOPdG adduct that presents a block to normal replication. We show here that yeast Rev1 incorporates the correct nucleotide C opposite a permanently ring-closed form of γ-HOPdG (PdG) with nearly the same efficiency as opposite an undamaged G. The structural basis of this action lies in the eviction of the PdG adduct from the Rev1 active site, and the pairing of incoming dCTP with a "surrogate" arginine residue. We also show that yeast Polζ can carry out the subsequent extension reaction. Together, our studies reveal how the exocyclic PdG adduct is accommodated in a DNA polymerase active site, and they show that the combined action of Rev1 and Polζ provides for accurate and efficient synthesis through this potentially carcinogenic DNA lesion.

Original languageEnglish (US)
Pages (from-to)239-245
Number of pages7
JournalStructure
Volume16
Issue number2
DOIs
StatePublished - Feb 12 2008

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Acrolein
DNA Adducts
DNA-Directed DNA Polymerase
Catalytic Domain
Yeasts
Environmental Pollutants
Guanine
Lipid Peroxidation
Arginine
Proteins
Nucleotides
DNA
2'-deoxycytidine 5'-triphosphate

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Protein-Template-Directed Synthesis across an Acrolein-Derived DNA Adduct by Yeast Rev1 DNA Polymerase. / Nair, Deepak T.; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

In: Structure, Vol. 16, No. 2, 12.02.2008, p. 239-245.

Research output: Contribution to journalArticle

Nair, Deepak T. ; Johnson, Robert E. ; Prakash, Louise ; Prakash, Satya ; Aggarwal, Aneel K. / Protein-Template-Directed Synthesis across an Acrolein-Derived DNA Adduct by Yeast Rev1 DNA Polymerase. In: Structure. 2008 ; Vol. 16, No. 2. pp. 239-245.
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