Crystal Structure of DNA Polymerase β with DNA Containing the Base Lesion Spiroiminodihydantoin in a Templating Position
Author(s) -
Brian E. Eckenroth,
Aaron M. Fleming,
Joann B. Sweasy,
Cynthia J. Burrows,
Sylvie Doublié
Publication year - 2014
Publication title -
biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.43
H-Index - 253
eISSN - 1520-4995
pISSN - 0006-2960
DOI - 10.1021/bi500270e
Subject(s) - dna , duplex (building) , base pair , crystallography , chemistry , dna polymerase , crystal structure , polymerase , ring (chemistry) , dna clamp , context (archaeology) , biophysics , stereochemistry , polymerase chain reaction , biology , gene , biochemistry , reverse transcriptase , organic chemistry , paleontology
The first high-resolution crystal structure of spiroiminodihydantoin (dSp1) was obtained in the context of the DNA polymerase β active site and reveals two areas of significance. First, the structure verifies the recently determined S configuration at the spirocyclic carbon. Second, the distortion of the DNA duplex is similar to that of the single-oxidation product 8-oxoguanine. For both oxidized lesions, adaptation of the syn conformation results in similar backbone distortions in the DNA duplex. The resulting conformation positions the dSp1 A-ring as the base-pairing face whereas the B-ring of dSp1 protrudes into the major groove.
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