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

J Mol Biol. 2011 Apr 29;408(2):252-61. doi: 10.1016/j.jmb.2011.02.042. Epub 2011 Feb 24.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Pairing
  • Crystallography, X-Ray
  • DNA Replication
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / metabolism
  • Humans
  • Models, Chemical
  • Protein Conformation
  • Pyrimidine Dimers / chemistry*
  • Pyrimidine Dimers / metabolism
  • Thymine / chemistry*
  • Thymine / metabolism
  • Ultraviolet Rays


  • Pyrimidine Dimers
  • DNA-Directed DNA Polymerase
  • POLK protein, human
  • Thymine

Associated data

  • PDB/3PZP