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PDBsum entry 3si8
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Transferase/DNA
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PDB id
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3si8
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References listed in PDB file
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Key reference
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Title
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Structure and mechanism of human DNA polymerase eta.
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Authors
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C.Biertümpfel,
Y.Zhao,
Y.Kondo,
S.Ramón-Maiques,
M.Gregory,
J.Y.Lee,
C.Masutani,
A.R.Lehmann,
F.Hanaoka,
W.Yang.
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Ref.
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Nature, 2010,
465,
1044-1048.
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PubMed id
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Abstract
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The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by
a deficiency in DNA polymerase eta (Poleta), a DNA polymerase that enables
replication through ultraviolet-induced pyrimidine dimers. Here we report
high-resolution crystal structures of human Poleta at four consecutive steps
during DNA synthesis through cis-syn cyclobutane thymine dimers. Poleta acts
like a 'molecular splint' to stabilize damaged DNA in a normal B-form
conformation. An enlarged active site accommodates the thymine dimer with
excellent stereochemistry for two-metal ion catalysis. Two residues conserved
among Poleta orthologues form specific hydrogen bonds with the lesion and the
incoming nucleotide to assist translesion synthesis. On the basis of the
structures, eight Poleta missense mutations causing XPV can be rationalized as
undermining the molecular splint or perturbing the active-site alignment. The
structures also provide an insight into the role of Poleta in replicating
through D loop and DNA fragile sites.
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