Cancer cells and tissues exhibit genome wide hypomethylation and regional hypermethylation. CpGmethylation of DNA (MeCpG-DNA) is defined as the formation of a C–C covalent bond between the 5′-C of cytosine and the –CH3 group of S-adenosylmethionine. Removal of the sole –CH3 group from the methylated cytosine of DNA is one of the many ways of DNAdemethylation, which contributes to activation of transcription. The mechanism of demethylation, the candidate enzyme(s) exhibiting direct demethylase activity and associated cofactors are not firmly established. Genomewide hypomethylation can be obtained in several ways by inactivation of DNMT enzyme activity, including covalent trapping of DNMT by cytosine base analogues. Removal of methyl layer could also be occurred by excision of the 5-methyl cytosine base by DNA glycosylases. The importance of truly chemically defined direct demethylation of intact DNA in regulation of gene expression, development, cell differentiation and transformation are discussed in this contribution.

Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development / PATRA S., K; Patra, A; Rizzi, Federica Maria Angela; GHOSH T., C; Bettuzzi, Saverio. - In: CANCER METASTASIS REVIEWS. - ISSN 0167-7659. - 27:(2008), pp. 315-334. [10.1007/s10555-008-9118-y]

Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development

RIZZI, Federica Maria Angela;BETTUZZI, Saverio
2008-01-01

Abstract

Cancer cells and tissues exhibit genome wide hypomethylation and regional hypermethylation. CpGmethylation of DNA (MeCpG-DNA) is defined as the formation of a C–C covalent bond between the 5′-C of cytosine and the –CH3 group of S-adenosylmethionine. Removal of the sole –CH3 group from the methylated cytosine of DNA is one of the many ways of DNAdemethylation, which contributes to activation of transcription. The mechanism of demethylation, the candidate enzyme(s) exhibiting direct demethylase activity and associated cofactors are not firmly established. Genomewide hypomethylation can be obtained in several ways by inactivation of DNMT enzyme activity, including covalent trapping of DNMT by cytosine base analogues. Removal of methyl layer could also be occurred by excision of the 5-methyl cytosine base by DNA glycosylases. The importance of truly chemically defined direct demethylation of intact DNA in regulation of gene expression, development, cell differentiation and transformation are discussed in this contribution.
Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development / PATRA S., K; Patra, A; Rizzi, Federica Maria Angela; GHOSH T., C; Bettuzzi, Saverio. - In: CANCER METASTASIS REVIEWS. - ISSN 0167-7659. - 27:(2008), pp. 315-334. [10.1007/s10555-008-9118-y]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1797001
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