Journal
NATURE
Volume 404, Issue 6781, Pages 1011-1013Publisher
MACMILLAN PUBLISHERS LTD
DOI: 10.1038/35010014
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A superfamily of DNA polymerases that bypass lesions in DNA has been described(1-4). Some family members are described as error-prone because mutations that inactivate the polymerase reduce damage-induced mutagenesis. In contrast, mutations in the skin cancer susceptibility gene XPV5,6, which encodes DNA polymerase (pol)-eta, lead to increased ultraviolet-induced mutagenesis(7-11). This, and the fact that pol-eta primarily inserts adenines during efficient bypass of thymine-thymine dimers in vitro(8,12,13), has led to the description of pol-eta as error-free. However, here we show that human pol-eta copies undamaged DNA with much lower fidelity than any other template-dependent DNA polymerase studied. Pol-eta lacks an intrinsic proofreading exonuclease activity and, depending on the mismatch, makes one base substitution error for every 18 to 380 nucleotides synthesized. This very low fidelity indicates a relaxed requirement for correct base pairing geometry and indicates that the function of pol-eta may be tightly controlled to prevent potentially mutagenic DNA synthesis.
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