Replication past a trans-4-hydroxynonenal minor-groove adduct by the sequential action of human DNA polymerases ι and κ

William T. Wolfle, Robert E. Johnson, Irina G. Minko, R. Stephen Lloyd, Satya Prakash, Louise Prakash

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The X-ray crystal structure of human DNA polymerase ι (Polι) has shown that it differs from all known Pols in its dependence upon Hoogsteen base pairing for synthesizing DNA. Hoogsteen base pairing provides an elegant mechanism for synthesizing DNA opposite minor-groove adducts that present a severe block to synthesis by replicative DNA polymerases. Germane to this problem, a variety of DNA adducts form at the N2 minor-groove position of guanine. Previously, we have shown that proficient and error-free replication through the γ-HOPdG (γ-hydroxy-1,N2-propano- 2′-deoxyguanosine) adduct, which is formed from the reaction of acrolein with the N2 of guanine, is mediated by the sequential action of human Polι and Polκ, in which Polι incorporates the nucleotide opposite the lesion site and Polκ carries out the subsequent extension reaction. To test the general applicability of these observations to other adducts formed at the N2 position of guanine, here we examine the proficiency of human Polι and Polκ to synthesize past stereoisomers of trans-4-hydroxy-2-nonenal-deoxyguanosine (HNE-dG). Even though HNE- and acrolein-modified dGs share common structural features, due to their increased size and other structural differences, HNE adducts are potentially more blocking for replication than γ-HOPdG. We show here that the sequential action of Polι and Polκ promotes efficient and error-free synthesis through the HNE-dG adducts, in which Polι incorporates the nucleotide opposite the lesion site and Polκ performs the extension reaction.

Original languageEnglish (US)
Pages (from-to)381-386
Number of pages6
JournalMolecular and Cellular Biology
Volume26
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Guanine
DNA-Directed DNA Polymerase
Acrolein
Deoxyguanosine
Base Pairing
Nucleotides
Stereoisomerism
DNA Adducts
DNA
X-Rays
4-hydroxy-2-nonenal

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Replication past a trans-4-hydroxynonenal minor-groove adduct by the sequential action of human DNA polymerases ι and κ. / Wolfle, William T.; Johnson, Robert E.; Minko, Irina G.; Lloyd, R. Stephen; Prakash, Satya; Prakash, Louise.

In: Molecular and Cellular Biology, Vol. 26, No. 1, 01.2006, p. 381-386.

Research output: Contribution to journalArticle

Wolfle, William T. ; Johnson, Robert E. ; Minko, Irina G. ; Lloyd, R. Stephen ; Prakash, Satya ; Prakash, Louise. / Replication past a trans-4-hydroxynonenal minor-groove adduct by the sequential action of human DNA polymerases ι and κ. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 1. pp. 381-386.
@article{0dcab93d20f248509c20a73048d76f7c,
title = "Replication past a trans-4-hydroxynonenal minor-groove adduct by the sequential action of human DNA polymerases ι and κ",
abstract = "The X-ray crystal structure of human DNA polymerase ι (Polι) has shown that it differs from all known Pols in its dependence upon Hoogsteen base pairing for synthesizing DNA. Hoogsteen base pairing provides an elegant mechanism for synthesizing DNA opposite minor-groove adducts that present a severe block to synthesis by replicative DNA polymerases. Germane to this problem, a variety of DNA adducts form at the N2 minor-groove position of guanine. Previously, we have shown that proficient and error-free replication through the γ-HOPdG (γ-hydroxy-1,N2-propano- 2′-deoxyguanosine) adduct, which is formed from the reaction of acrolein with the N2 of guanine, is mediated by the sequential action of human Polι and Polκ, in which Polι incorporates the nucleotide opposite the lesion site and Polκ carries out the subsequent extension reaction. To test the general applicability of these observations to other adducts formed at the N2 position of guanine, here we examine the proficiency of human Polι and Polκ to synthesize past stereoisomers of trans-4-hydroxy-2-nonenal-deoxyguanosine (HNE-dG). Even though HNE- and acrolein-modified dGs share common structural features, due to their increased size and other structural differences, HNE adducts are potentially more blocking for replication than γ-HOPdG. We show here that the sequential action of Polι and Polκ promotes efficient and error-free synthesis through the HNE-dG adducts, in which Polι incorporates the nucleotide opposite the lesion site and Polκ performs the extension reaction.",
author = "Wolfle, {William T.} and Johnson, {Robert E.} and Minko, {Irina G.} and Lloyd, {R. Stephen} and Satya Prakash and Louise Prakash",
year = "2006",
month = "1",
doi = "10.1128/MCB.26.1.381-386.2006",
language = "English (US)",
volume = "26",
pages = "381--386",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - Replication past a trans-4-hydroxynonenal minor-groove adduct by the sequential action of human DNA polymerases ι and κ

AU - Wolfle, William T.

AU - Johnson, Robert E.

AU - Minko, Irina G.

AU - Lloyd, R. Stephen

AU - Prakash, Satya

AU - Prakash, Louise

PY - 2006/1

Y1 - 2006/1

N2 - The X-ray crystal structure of human DNA polymerase ι (Polι) has shown that it differs from all known Pols in its dependence upon Hoogsteen base pairing for synthesizing DNA. Hoogsteen base pairing provides an elegant mechanism for synthesizing DNA opposite minor-groove adducts that present a severe block to synthesis by replicative DNA polymerases. Germane to this problem, a variety of DNA adducts form at the N2 minor-groove position of guanine. Previously, we have shown that proficient and error-free replication through the γ-HOPdG (γ-hydroxy-1,N2-propano- 2′-deoxyguanosine) adduct, which is formed from the reaction of acrolein with the N2 of guanine, is mediated by the sequential action of human Polι and Polκ, in which Polι incorporates the nucleotide opposite the lesion site and Polκ carries out the subsequent extension reaction. To test the general applicability of these observations to other adducts formed at the N2 position of guanine, here we examine the proficiency of human Polι and Polκ to synthesize past stereoisomers of trans-4-hydroxy-2-nonenal-deoxyguanosine (HNE-dG). Even though HNE- and acrolein-modified dGs share common structural features, due to their increased size and other structural differences, HNE adducts are potentially more blocking for replication than γ-HOPdG. We show here that the sequential action of Polι and Polκ promotes efficient and error-free synthesis through the HNE-dG adducts, in which Polι incorporates the nucleotide opposite the lesion site and Polκ performs the extension reaction.

AB - The X-ray crystal structure of human DNA polymerase ι (Polι) has shown that it differs from all known Pols in its dependence upon Hoogsteen base pairing for synthesizing DNA. Hoogsteen base pairing provides an elegant mechanism for synthesizing DNA opposite minor-groove adducts that present a severe block to synthesis by replicative DNA polymerases. Germane to this problem, a variety of DNA adducts form at the N2 minor-groove position of guanine. Previously, we have shown that proficient and error-free replication through the γ-HOPdG (γ-hydroxy-1,N2-propano- 2′-deoxyguanosine) adduct, which is formed from the reaction of acrolein with the N2 of guanine, is mediated by the sequential action of human Polι and Polκ, in which Polι incorporates the nucleotide opposite the lesion site and Polκ carries out the subsequent extension reaction. To test the general applicability of these observations to other adducts formed at the N2 position of guanine, here we examine the proficiency of human Polι and Polκ to synthesize past stereoisomers of trans-4-hydroxy-2-nonenal-deoxyguanosine (HNE-dG). Even though HNE- and acrolein-modified dGs share common structural features, due to their increased size and other structural differences, HNE adducts are potentially more blocking for replication than γ-HOPdG. We show here that the sequential action of Polι and Polκ promotes efficient and error-free synthesis through the HNE-dG adducts, in which Polι incorporates the nucleotide opposite the lesion site and Polκ performs the extension reaction.

UR - http://www.scopus.com/inward/record.url?scp=33645241164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645241164&partnerID=8YFLogxK

U2 - 10.1128/MCB.26.1.381-386.2006

DO - 10.1128/MCB.26.1.381-386.2006

M3 - Article

VL - 26

SP - 381

EP - 386

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 1

ER -