Thymine-DNA glycosylase and G to A transition mutations at CpG sites

About 23% of mutations in hereditary human diseases and 24% of mutations in p53 in human cancers are G to A transitions at sites of cytosine methylation suggesting that these sites are either foci for DNA damage, or foci for damage that is poorly repaired. Thymine produced at these sites by the hydr...

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Bibliographic Details
Published in:Mutation research. Reviews in mutation research 2000-04, Vol.462 (2), p.137-147
Main Authors: Waters, Timothy R, Swann, Peter F
Format: Article
Language:English
Subjects:
3,N@@u4@-ethenocytosine
5-methylcytosine
5-Methylcytosine deamination
Apurinic endonuclease HAP1
Base excision repair
DNA repair
p53 gene
p53 Mutation spectra
thymine
Thymine-DNA glycosylase
transition mutation
uracil
Uracil-DNA glycosylase
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Summary:About 23% of mutations in hereditary human diseases and 24% of mutations in p53 in human cancers are G to A transitions at sites of cytosine methylation suggesting that these sites are either foci for DNA damage, or foci for damage that is poorly repaired. Thymine produced at these sites by the hydrolytic deamination of 5-methylcytosine is removed by thymine-DNA glycosylase. Thymine-DNA glycosylase will also remove 3, N 4-ethenocytosine and uracil from DNA. The action of this enzyme is limited by its very low k cat and by tight binding to the apurinic site produced when the thymine is removed. These properties of the enzyme suggest that the inefficiency of the base excision repair pathway that it initiates may be the underlying cause of the prevalence of these mutations.
ISSN:1383-5742
1388-2139
DOI:10.1016/S1383-5742(00)00031-4