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

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 ? (Pol?), 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 Pol? 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 Pol? in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.

SUBMITTER: Vasquez-Del Carpio R

PROVIDER: S-EPMC3093752 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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

Vasquez-Del Carpio Rodrigo R Silverstein Timothy D TD Lone Samer S Johnson Robert E RE Prakash Louise L Prakash Satya S Aggarwal Aneel K AK

Journal of molecular biology 20110224 2

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 ...[more]

PMID: 21354175

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