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PDBsum entry 6p1v
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References listed in PDB file
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Key reference
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Title
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Unexpected behavior of DNA polymerase mu opposite template 8-Oxo-7,8-Dihydro-2'-Guanosine.
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Authors
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A.M.Kaminski,
K.K.Chiruvella,
D.A.Ramsden,
T.A.Kunkel,
K.Bebenek,
L.C.Pedersen.
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Ref.
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Nucleic Acids Res, 2019,
47,
9410-9422.
[DOI no: ]
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PubMed id
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Abstract
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DNA double-strand breaks (DSBs) resulting from reactive oxygen species generated
by exposure to UV and ionizing radiation are characterized by clusters of
lesions near break sites. Such complex DSBs are repaired slowly, and their
persistence can have severe consequences for human health. We have therefore
probed DNA break repair containing a template 8-oxo-7,8-dihydro-2'-guanosine
(8OG) by Family X Polymerase μ (Pol μ) in steady-state kinetics and cell-based
assays. Pol μ tolerates 8OG-containing template DNA substrates, and the filled
products can be subsequently ligated by DNA Ligase IV during Nonhomologous
end-joining. Furthermore, Pol μ exhibits a strong preference for mutagenic
bypass of 8OG by insertion of adenine. Crystal structures reveal that the
template 8OG is accommodated in the Pol μ active site with none of the DNA
substrate distortions observed for Family X siblings Pols β or λ. Kinetic
characterization of template 8OG bypass indicates that Pol μ inserts adenosine
nucleotides with weak sugar selectivity and, given the high cellular
concentration of ATP, likely performs its role in repair of complex
8OG-containing DSBs using ribonucleotides.
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