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

Role of human DNA polymerase κ in extension opposite from a cis-syn thymine dimer.
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人类 DNA 聚合酶 γ 在与顺式胸腺嘧啶二聚体相反的延伸中的作用。

DOI:
10.1016/j.jmb.2011.02.042
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发表时间:
2011
影响因子:
5.6
通讯作者:
Aggarwal,AneelK
Aggarwal,AneelK
中科院分区:
生物学2区
文献类型:
--
作者:
Vasquez-DelCarpio,Rodrigo;Silverstein,TimothyD;Lone,Samer;Johnson,RobertE;Prakash,Louise;Prakash,Satya;Aggarwal,AneelK

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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.