作者
Vera Gorbunova, Andrei Seluanov, David Mittelman, John H Wilson
发表日期
2004/12/1
期刊
Human molecular genetics
卷号
13
期号
23
页码范围
2979-2989
出版商
Oxford University Press
简介
Many neurological diseases, including myotonic dystrophy, Huntington's disease and several spinocerebellar ataxias, result from intergenerational increases in the length of a CTG·CAG repeat tract. Although the basis for intergenerational repeat expansion is unclear, repeat tracts are especially unstable during germline development and production of gametes. Mammalian development is characterized by waves of genome-wide demethylation and remethylation. To test whether changes in methylation status might contribute to trinucleotide repeat instability, we examined the effects of DNA methyltransferase inhibitors on trinucleotide repeat stability in mammalian cells. Using a selectable genetic system for detection of repeat contractions in CHO cells, we showed that the rate of contractions increased >1000-fold upon treatment with the DNA methyltransferase inhibitor 5-aza-deoxycytidine (5-aza-CdR). The …
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V Gorbunova, A Seluanov, D Mittelman, JH Wilson - Human molecular genetics, 2004