Human DINB1-encoded DNA polymerase κ is a promiscuous extender of mispaired primer termini

M. Todd Washington, Robert E. Johnson, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Both in yeast and humans, DNA polymerase (Pol) η functions in the error-free replication of UV-damaged DNA, and Polη has the unique ability to efficiently replicate through a cis-syn thymine-thymine (T-T) dimer by inserting two As opposite the two Ts of the dimer. Although human DINB1-encoded Polκ belongs to the same protein family as Polη, Polκ shows no ability to bypass this DNA lesion and its biological function has remained unclear. Here, we examine Polκ for its ability to extend from primer-terminal mispairs opposite nondamaged and damaged DNA templates. We find that Polκ is a promiscuous extender of primer-terminal mispairs opposite nondamaged DNA templates, and interestingly, it is also very efficient at extending from a G opposite the 3′T of a T-T dimer. These observations provide biochemical evidence for a role of Polκ in the extension of mismatched base pairs during normal DNA replication, and in addition, they implicate Polκ in the mutagenic bypass of T-T dimers. In its proficient mismatch extension ability, Polκ is more similar to the unrelated DNA polymerase ζ than it is to the phylogenetically related Polη or Polι. Thus, in humans, Polκ would compete with Polζ for the extension of mismatched base pairs on damaged and undamaged DNAs.

Original languageEnglish (US)
Pages (from-to)1910-1914
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number4
DOIs
StatePublished - Feb 19 2002

Fingerprint

DNA-Directed DNA Polymerase
Pyrimidine Dimers
Thymine
DNA
Base Pairing
DNA Replication
Yeasts
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Human DINB1-encoded DNA polymerase κ is a promiscuous extender of mispaired primer termini. / Washington, M. Todd; Johnson, Robert E.; Prakash, Louise; Prakash, Satya.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 4, 19.02.2002, p. 1910-1914.

Research output: Contribution to journalArticle

@article{4cf396ff89c840199ef12a783345bb57,
title = "Human DINB1-encoded DNA polymerase κ is a promiscuous extender of mispaired primer termini",
abstract = "Both in yeast and humans, DNA polymerase (Pol) η functions in the error-free replication of UV-damaged DNA, and Polη has the unique ability to efficiently replicate through a cis-syn thymine-thymine (T-T) dimer by inserting two As opposite the two Ts of the dimer. Although human DINB1-encoded Polκ belongs to the same protein family as Polη, Polκ shows no ability to bypass this DNA lesion and its biological function has remained unclear. Here, we examine Polκ for its ability to extend from primer-terminal mispairs opposite nondamaged and damaged DNA templates. We find that Polκ is a promiscuous extender of primer-terminal mispairs opposite nondamaged DNA templates, and interestingly, it is also very efficient at extending from a G opposite the 3′T of a T-T dimer. These observations provide biochemical evidence for a role of Polκ in the extension of mismatched base pairs during normal DNA replication, and in addition, they implicate Polκ in the mutagenic bypass of T-T dimers. In its proficient mismatch extension ability, Polκ is more similar to the unrelated DNA polymerase ζ than it is to the phylogenetically related Polη or Polι. Thus, in humans, Polκ would compete with Polζ for the extension of mismatched base pairs on damaged and undamaged DNAs.",
author = "Washington, {M. Todd} and Johnson, {Robert E.} and Louise Prakash and Satya Prakash",
year = "2002",
month = "2",
day = "19",
doi = "10.1073/pnas.032594399",
language = "English (US)",
volume = "99",
pages = "1910--1914",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "4",

}

TY - JOUR

T1 - Human DINB1-encoded DNA polymerase κ is a promiscuous extender of mispaired primer termini

AU - Washington, M. Todd

AU - Johnson, Robert E.

AU - Prakash, Louise

AU - Prakash, Satya

PY - 2002/2/19

Y1 - 2002/2/19

N2 - Both in yeast and humans, DNA polymerase (Pol) η functions in the error-free replication of UV-damaged DNA, and Polη has the unique ability to efficiently replicate through a cis-syn thymine-thymine (T-T) dimer by inserting two As opposite the two Ts of the dimer. Although human DINB1-encoded Polκ belongs to the same protein family as Polη, Polκ shows no ability to bypass this DNA lesion and its biological function has remained unclear. Here, we examine Polκ for its ability to extend from primer-terminal mispairs opposite nondamaged and damaged DNA templates. We find that Polκ is a promiscuous extender of primer-terminal mispairs opposite nondamaged DNA templates, and interestingly, it is also very efficient at extending from a G opposite the 3′T of a T-T dimer. These observations provide biochemical evidence for a role of Polκ in the extension of mismatched base pairs during normal DNA replication, and in addition, they implicate Polκ in the mutagenic bypass of T-T dimers. In its proficient mismatch extension ability, Polκ is more similar to the unrelated DNA polymerase ζ than it is to the phylogenetically related Polη or Polι. Thus, in humans, Polκ would compete with Polζ for the extension of mismatched base pairs on damaged and undamaged DNAs.

AB - Both in yeast and humans, DNA polymerase (Pol) η functions in the error-free replication of UV-damaged DNA, and Polη has the unique ability to efficiently replicate through a cis-syn thymine-thymine (T-T) dimer by inserting two As opposite the two Ts of the dimer. Although human DINB1-encoded Polκ belongs to the same protein family as Polη, Polκ shows no ability to bypass this DNA lesion and its biological function has remained unclear. Here, we examine Polκ for its ability to extend from primer-terminal mispairs opposite nondamaged and damaged DNA templates. We find that Polκ is a promiscuous extender of primer-terminal mispairs opposite nondamaged DNA templates, and interestingly, it is also very efficient at extending from a G opposite the 3′T of a T-T dimer. These observations provide biochemical evidence for a role of Polκ in the extension of mismatched base pairs during normal DNA replication, and in addition, they implicate Polκ in the mutagenic bypass of T-T dimers. In its proficient mismatch extension ability, Polκ is more similar to the unrelated DNA polymerase ζ than it is to the phylogenetically related Polη or Polι. Thus, in humans, Polκ would compete with Polζ for the extension of mismatched base pairs on damaged and undamaged DNAs.

UR - http://www.scopus.com/inward/record.url?scp=0037133339&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037133339&partnerID=8YFLogxK

U2 - 10.1073/pnas.032594399

DO - 10.1073/pnas.032594399

M3 - Article

C2 - 11842189

AN - SCOPUS:0037133339

VL - 99

SP - 1910

EP - 1914

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 - 4

ER -