Role of human DNA polymerase κ as an extender in translesion synthesis

L. Haracska, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Human DNA polymerase(Pol)Κ is a member of the Y family of DNA polymerases. Unlike Polε, another member of this family, which carries out efficient translesion synthesis through various DNA lesions, the role of PolΚ in lesion bypass has remained unclear. Recent studies, however, have indicated that PolΚ is a proficient extender of mispaired primer termini on undamaged DNAs and also on cis-syn thymine-thymine (T-T) dimer-containing DNA. Here we determine whether PolΚ can promote the efficient bypass of DNA lesions by extending from the nucleotides inserted opposite the lesion site by another DNA polymerase. From steady-state kinetic analyses, we find that PolΚ is highly inefficient at incorporating nucleotides opposite an O6-methyl guanine (m6G) lesion, but it efficiently extends from the T or C nucleotide incorporated opposite this lesion by Polδ. Opposite an 8-oxoguanine (8-oxoG) lesion, PolΚ efficiently inserts an A and then proficiently extends from it. Importantly, for both these DNA lesions, however, the most efficient bypass occurs when Polδ is combined with PolΚ; in this reaction, PolΚ performs the extension step after the incorporation of nucleotides opposite these lesion sites by Polδ. These studies reveal a role for PolΚ in the extension phase of lesion bypass.

Original languageEnglish
Pages (from-to)16000-16005
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number25
DOIs
Publication statusPublished - Dec 10 2002

Fingerprint

DNA-Directed DNA Polymerase
Nucleotides
DNA
Pyrimidine Dimers
Thymine
Guanine

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Role of human DNA polymerase κ as an extender in translesion synthesis. / Haracska, L.; Prakash, Louise; Prakash, Satya.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 25, 10.12.2002, p. 16000-16005.

Research output: Contribution to journalArticle

@article{43b07ada96534dd48c0916dfb0a68e19,
title = "Role of human DNA polymerase κ as an extender in translesion synthesis",
abstract = "Human DNA polymerase(Pol)Κ is a member of the Y family of DNA polymerases. Unlike Polε, another member of this family, which carries out efficient translesion synthesis through various DNA lesions, the role of PolΚ in lesion bypass has remained unclear. Recent studies, however, have indicated that PolΚ is a proficient extender of mispaired primer termini on undamaged DNAs and also on cis-syn thymine-thymine (T-T) dimer-containing DNA. Here we determine whether PolΚ can promote the efficient bypass of DNA lesions by extending from the nucleotides inserted opposite the lesion site by another DNA polymerase. From steady-state kinetic analyses, we find that PolΚ is highly inefficient at incorporating nucleotides opposite an O6-methyl guanine (m6G) lesion, but it efficiently extends from the T or C nucleotide incorporated opposite this lesion by Polδ. Opposite an 8-oxoguanine (8-oxoG) lesion, PolΚ efficiently inserts an A and then proficiently extends from it. Importantly, for both these DNA lesions, however, the most efficient bypass occurs when Polδ is combined with PolΚ; in this reaction, PolΚ performs the extension step after the incorporation of nucleotides opposite these lesion sites by Polδ. These studies reveal a role for PolΚ in the extension phase of lesion bypass.",
author = "L. Haracska and Louise Prakash and Satya Prakash",
year = "2002",
month = "12",
day = "10",
doi = "10.1073/pnas.252524999",
language = "English",
volume = "99",
pages = "16000--16005",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "25",

}

TY - JOUR

T1 - Role of human DNA polymerase κ as an extender in translesion synthesis

AU - Haracska, L.

AU - Prakash, Louise

AU - Prakash, Satya

PY - 2002/12/10

Y1 - 2002/12/10

N2 - Human DNA polymerase(Pol)Κ is a member of the Y family of DNA polymerases. Unlike Polε, another member of this family, which carries out efficient translesion synthesis through various DNA lesions, the role of PolΚ in lesion bypass has remained unclear. Recent studies, however, have indicated that PolΚ is a proficient extender of mispaired primer termini on undamaged DNAs and also on cis-syn thymine-thymine (T-T) dimer-containing DNA. Here we determine whether PolΚ can promote the efficient bypass of DNA lesions by extending from the nucleotides inserted opposite the lesion site by another DNA polymerase. From steady-state kinetic analyses, we find that PolΚ is highly inefficient at incorporating nucleotides opposite an O6-methyl guanine (m6G) lesion, but it efficiently extends from the T or C nucleotide incorporated opposite this lesion by Polδ. Opposite an 8-oxoguanine (8-oxoG) lesion, PolΚ efficiently inserts an A and then proficiently extends from it. Importantly, for both these DNA lesions, however, the most efficient bypass occurs when Polδ is combined with PolΚ; in this reaction, PolΚ performs the extension step after the incorporation of nucleotides opposite these lesion sites by Polδ. These studies reveal a role for PolΚ in the extension phase of lesion bypass.

AB - Human DNA polymerase(Pol)Κ is a member of the Y family of DNA polymerases. Unlike Polε, another member of this family, which carries out efficient translesion synthesis through various DNA lesions, the role of PolΚ in lesion bypass has remained unclear. Recent studies, however, have indicated that PolΚ is a proficient extender of mispaired primer termini on undamaged DNAs and also on cis-syn thymine-thymine (T-T) dimer-containing DNA. Here we determine whether PolΚ can promote the efficient bypass of DNA lesions by extending from the nucleotides inserted opposite the lesion site by another DNA polymerase. From steady-state kinetic analyses, we find that PolΚ is highly inefficient at incorporating nucleotides opposite an O6-methyl guanine (m6G) lesion, but it efficiently extends from the T or C nucleotide incorporated opposite this lesion by Polδ. Opposite an 8-oxoguanine (8-oxoG) lesion, PolΚ efficiently inserts an A and then proficiently extends from it. Importantly, for both these DNA lesions, however, the most efficient bypass occurs when Polδ is combined with PolΚ; in this reaction, PolΚ performs the extension step after the incorporation of nucleotides opposite these lesion sites by Polδ. These studies reveal a role for PolΚ in the extension phase of lesion bypass.

UR - http://www.scopus.com/inward/record.url?scp=0037058976&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037058976&partnerID=8YFLogxK

U2 - 10.1073/pnas.252524999

DO - 10.1073/pnas.252524999

M3 - Article

VL - 99

SP - 16000

EP - 16005

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 25

ER -