Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases ι and κ

M. Todd Washington, Irina G. Minko, Robert E. Johnson, William T. Wolfle, Thomas M. Harris, R. Stephen Lloyd, Satya Prakash, Louise Prakash

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

DNA polymerase ι (Polι) is a member of the Y family of DNA polymerases, which promote replication through DNA lesions. The role of Polι in lesion bypass, however, has remained unclear. Polι is highly unusual in that it incorporates nucleotides opposite different template bases with very different efficiencies and fidelities. Since interactions of DNA polymerases with the DNA minor groove provide for the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, we considered the possibility that Polι differs from other DNA polymerases in not being as sensitive to distortions of the minor groove at the site of the incipient base pair and that this enables it to incorporate nucleotides opposite highly distorting minor-groove DNA adducts. To check the validity of this idea, we examined whether Polι could incorporate nucleotides opposite the γ-HOPdG adduct, which is formed from an initial reaction of acrolein with the N2 of guanine. We show here that Polι incorporates a C opposite this adduct with nearly the same efficiency as it does opposite a nonadducted template G residue. The subsequent extension step, however, is performed by Polκ, which efficiently extends from the C incorporated opposite the adduct. Based upon these observations, we suggest that an important biological role of Polι and Polκ is to act sequentially to carry out the efficient and accurate bypass of highly distorting minor-groove DNA adducts of the purine bases.

Original languageEnglish (US)
Pages (from-to)5687-5693
Number of pages7
JournalMolecular and Cellular Biology
Volume24
Issue number13
DOIs
StatePublished - Jul 2004

Fingerprint

DNA Adducts
DNA-Directed DNA Polymerase
Nucleotides
Acrolein
Guanine
DNA Replication
Base Pairing
DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases ι and κ. / Washington, M. Todd; Minko, Irina G.; Johnson, Robert E.; Wolfle, William T.; Harris, Thomas M.; Lloyd, R. Stephen; Prakash, Satya; Prakash, Louise.

In: Molecular and Cellular Biology, Vol. 24, No. 13, 07.2004, p. 5687-5693.

Research output: Contribution to journalArticle

Washington, M. Todd ; Minko, Irina G. ; Johnson, Robert E. ; Wolfle, William T. ; Harris, Thomas M. ; Lloyd, R. Stephen ; Prakash, Satya ; Prakash, Louise. / Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases ι and κ. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 13. pp. 5687-5693.
@article{f0370520d496418da574a812bd9e850f,
title = "Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases ι and κ",
abstract = "DNA polymerase ι (Polι) is a member of the Y family of DNA polymerases, which promote replication through DNA lesions. The role of Polι in lesion bypass, however, has remained unclear. Polι is highly unusual in that it incorporates nucleotides opposite different template bases with very different efficiencies and fidelities. Since interactions of DNA polymerases with the DNA minor groove provide for the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, we considered the possibility that Polι differs from other DNA polymerases in not being as sensitive to distortions of the minor groove at the site of the incipient base pair and that this enables it to incorporate nucleotides opposite highly distorting minor-groove DNA adducts. To check the validity of this idea, we examined whether Polι could incorporate nucleotides opposite the γ-HOPdG adduct, which is formed from an initial reaction of acrolein with the N2 of guanine. We show here that Polι incorporates a C opposite this adduct with nearly the same efficiency as it does opposite a nonadducted template G residue. The subsequent extension step, however, is performed by Polκ, which efficiently extends from the C incorporated opposite the adduct. Based upon these observations, we suggest that an important biological role of Polι and Polκ is to act sequentially to carry out the efficient and accurate bypass of highly distorting minor-groove DNA adducts of the purine bases.",
author = "Washington, {M. Todd} and Minko, {Irina G.} and Johnson, {Robert E.} and Wolfle, {William T.} and Harris, {Thomas M.} and Lloyd, {R. Stephen} and Satya Prakash and Louise Prakash",
year = "2004",
month = "7",
doi = "10.1128/MCB.24.13.5687-5693.2004",
language = "English (US)",
volume = "24",
pages = "5687--5693",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "13",

}

TY - JOUR

T1 - Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases ι and κ

AU - Washington, M. Todd

AU - Minko, Irina G.

AU - Johnson, Robert E.

AU - Wolfle, William T.

AU - Harris, Thomas M.

AU - Lloyd, R. Stephen

AU - Prakash, Satya

AU - Prakash, Louise

PY - 2004/7

Y1 - 2004/7

N2 - DNA polymerase ι (Polι) is a member of the Y family of DNA polymerases, which promote replication through DNA lesions. The role of Polι in lesion bypass, however, has remained unclear. Polι is highly unusual in that it incorporates nucleotides opposite different template bases with very different efficiencies and fidelities. Since interactions of DNA polymerases with the DNA minor groove provide for the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, we considered the possibility that Polι differs from other DNA polymerases in not being as sensitive to distortions of the minor groove at the site of the incipient base pair and that this enables it to incorporate nucleotides opposite highly distorting minor-groove DNA adducts. To check the validity of this idea, we examined whether Polι could incorporate nucleotides opposite the γ-HOPdG adduct, which is formed from an initial reaction of acrolein with the N2 of guanine. We show here that Polι incorporates a C opposite this adduct with nearly the same efficiency as it does opposite a nonadducted template G residue. The subsequent extension step, however, is performed by Polκ, which efficiently extends from the C incorporated opposite the adduct. Based upon these observations, we suggest that an important biological role of Polι and Polκ is to act sequentially to carry out the efficient and accurate bypass of highly distorting minor-groove DNA adducts of the purine bases.

AB - DNA polymerase ι (Polι) is a member of the Y family of DNA polymerases, which promote replication through DNA lesions. The role of Polι in lesion bypass, however, has remained unclear. Polι is highly unusual in that it incorporates nucleotides opposite different template bases with very different efficiencies and fidelities. Since interactions of DNA polymerases with the DNA minor groove provide for the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, we considered the possibility that Polι differs from other DNA polymerases in not being as sensitive to distortions of the minor groove at the site of the incipient base pair and that this enables it to incorporate nucleotides opposite highly distorting minor-groove DNA adducts. To check the validity of this idea, we examined whether Polι could incorporate nucleotides opposite the γ-HOPdG adduct, which is formed from an initial reaction of acrolein with the N2 of guanine. We show here that Polι incorporates a C opposite this adduct with nearly the same efficiency as it does opposite a nonadducted template G residue. The subsequent extension step, however, is performed by Polκ, which efficiently extends from the C incorporated opposite the adduct. Based upon these observations, we suggest that an important biological role of Polι and Polκ is to act sequentially to carry out the efficient and accurate bypass of highly distorting minor-groove DNA adducts of the purine bases.

UR - http://www.scopus.com/inward/record.url?scp=2942753954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942753954&partnerID=8YFLogxK

U2 - 10.1128/MCB.24.13.5687-5693.2004

DO - 10.1128/MCB.24.13.5687-5693.2004

M3 - Article

C2 - 15199127

AN - SCOPUS:2942753954

VL - 24

SP - 5687

EP - 5693

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 13

ER -