Specificity of Human Thymine DNA Glycosylase Depends onN-Glycosidic Bond Stability
نویسندگان
چکیده
منابع مشابه
Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA
Human thymine DNA glycosylase (hTDG) efficiently excises 5-carboxylcytosine (5caC), a key oxidation product of 5-methylcytosine in genomic DNA, in a recently discovered cytosine demethylation pathway. We present here the crystal structures of the hTDG catalytic domain in complex with duplex DNA containing either 5caC or a fluorinated analog. These structures, together with biochemical and compu...
متن کاملKinetics of the action of thymine DNA glycosylase.
The time course of removal of thymine by thymine DNA glycosylase has been measured in vitro. Each molecule of thymine DNA glycosylase removes only one molecule of thymine from DNA containing a G.T mismatch because it binds tightly to the apurinic DNA site left after removal of thymine. The 5'-flanking base pair to G.T mismatches influences the rate of removal of thymine: kcat values with C.G, T...
متن کاملStability of DNA thymine hydrates.
Pyrimidine hydrates are products of ultraviolet irradiation of DNA. We have already demonstrated the formation of both cis-thymine hydrate and trans-thymine hydrate (6-hydroxy-5,6-dihydrothymine) in irradiated poly(dA-dT):poly(dA-dT). These are released from DNA as free bases by bacterial or human glycosylases. Thymine hydrate stabilities were studied in irradiated DNA substrates using purified...
متن کاملCrystal structure of human thymine DNA glycosylase bound to DNA elucidates sequence-specific mismatch recognition.
Cytosine methylation at CpG dinucleotides produces m(5)CpG, an epigenetic modification that is important for transcriptional regulation and genomic stability in vertebrate cells. However, m(5)C deamination yields mutagenic G.T mispairs, which are implicated in genetic disease, cancer, and aging. Human thymine DNA glycosylase (hTDG) removes T from G.T mispairs, producing an abasic (or AP) site, ...
متن کاملFunctionality of Human Thymine DNA Glycosylase Requires SUMO-Regulated Changes in Protein Conformation
BACKGROUND Base excision repair initiated by human thymine-DNA glycosylase (TDG) results in the generation of abasic sites (AP sites) in DNA. TDG remains bound to this unstable repair intermediate, indicating that its transmission to the downstream-acting AP endonuclease is a coordinated process. Previously, we established that posttranslational modification of TDG with Small Ubiquitin-like MOd...
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ژورنال
عنوان ژورنال: Journal of the American Chemical Society
سال: 2006
ISSN: 0002-7863,1520-5126
DOI: 10.1021/ja0634829