Role of human DNA polymerase κ in extension opposite from a cis-syn thymine dimer

Rodrigo Vasquez-Del Carpio, Timothy D. Silverstein, Samer Lone, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Exposure of DNA to UV radiation causes covalent linkages between adjacent pyrimidines. The most common lesion found in DNA from these UV-induced linkages is the cis-syn cyclobutane pyrimidine dimer. Human DNA polymerase κ (Polκ), a member of the Y-family of DNA polymerases, is unable to insert nucleotides opposite the 3′T of a cis-syn T-T dimer, but it can efficiently extend from a nucleotide inserted opposite the 3′T of the dimer by another DNA polymerase. We present here the structure of human Polκ in the act of inserting a nucleotide opposite the 5′T of the cis-syn T-T dimer. The structure reveals a constrained active-site cleft that is unable to accommodate the 3′T of a cis-syn T-T dimer but is remarkably well adapted to accommodate the 5′T via Watson-Crick base pairing, in accord with a proposed role for Polκ in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.

Original languageEnglish (US)
Pages (from-to)252-261
Number of pages10
JournalJournal of Molecular Biology
Volume408
Issue number2
DOIs
StatePublished - Apr 29 2011

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Keywords

  • DNA polymerase
  • DNA repair
  • UV DNA damage
  • Y-family
  • translesion DNA synthesis

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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