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

Journal Article · Tue Jul 08 04:00:00 EDT 2008 · Structure

DOI:https://doi.org/10.1016/j.str.2007.12.009· OSTI ID:1006708

Nair, Deepak T; Johnson, Robert E; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K ^[1]

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1. Sinai

Acrolein is generated as the end product of lipid peroxidation and is also a ubiquitous environmental pollutant. Its reaction with the N{sup 2} of guanine leads to a cyclic {gamma}-HOPdG adduct that presents a block to normal replication. We show here the yeast Rev1 incorporates the correct nucleotide C opposite a permanently ring-closed form of {gamma}-HOPdG (PdG) with nearly the same efficiency as opposite an undamaged G. The structural bais of this action lies in the eviction of PdG adduct from the Rev1 active site, and the pairing of incoming dCTP with a surrogate' arginine residue. We also show that yeast Pol{zeta} 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 Pol{zeta} provides for accurate and efficient synthesis through this potentially carcinogenic DNA lesion.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006708
• Journal Information: Structure, Journal Name: Structure Journal Issue: (2) ; 02, 2008 Vol. 16
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ACROLEIN
ADDUCTS
ARGININE
DNA
DNA ADDUCTS
DNA POLYMERASES
EFFICIENCY
GUANINE
LIPIDS
NUCLEOTIDES
SYNTHESIS
YEASTS