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

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

Author information

1
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA.

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.

PMID:
21354175
PMCID:
PMC3093752
DOI:
10.1016/j.jmb.2011.02.042
[Indexed for MEDLINE]
Free PMC Article

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