DNA methylation in cancer development, diagnosis and therapy-multiple opportunities for genotoxic agents to act as methylome disruptors or remediators - Publikacja - MOST Wiedzy

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DNA methylation in cancer development, diagnosis and therapy-multiple opportunities for genotoxic agents to act as methylome disruptors or remediators

Abstrakt

The role of DNA methylation and recently discovered hydroxymethylation in the function of the human epigenome is currently one of the hottest topics in the life sciences. Progress in this field of research has been further accelerated by the discovery that alterations in the methylome are not only associated with key functions of cells and organisms, such as development, differentiation and gene expression, but may underlie a number of human diseases, including cancer. This review describes both well established and more recent observations concerning alterations in the methylome, i.e. the global and local distribution of 5-methylcytosines, involved in its normal functions. Then, the changes in DNA methylation pattern seen in cancer cells are discussed in the context of their utilisation in cancer diagnostics and treatment. On this basis, comparisons are made between natural covalent DNA modification and that induced by genotoxic agents, chemical carcinogens and antitumour drugs as regards their impact on epigenetic mechanisms. The available data suggest that DNA damage by genotoxins can mimic epigenetic markers and in consequence disrupt the proper function of the epigenome. On the other hand, the same processes in cancer cells, e.g. DNA demethylation as a result of DNA methyltransferase blocking or the induction of DNA repair by DNA adducts, may restore the activity of hypermethylated anticancer genes. The observed multiple mechanisms by which genotoxic agents directly affect methylome function suggest that chemical carcinogens act primarily as epigenome disruptors, whereas mutations are secondary events that occur at later stages of cancer development when genomeprotecting mechanisms have already been deregulated.

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Informacje szczegółowe

Kategoria:
Publikacja w czasopiśmie
Typ:
artykuł w czasopiśmie wyróżnionym w JCR
Opublikowano w:
MUTAGENESIS nr 26, strony 475 - 487,
ISSN: 0267-8357
Język:
angielski
Rok wydania:
2011
Opis bibliograficzny:
Lewandowska J., Bartoszek-Pączkowska A.: DNA methylation in cancer development, diagnosis and therapy-multiple opportunities for genotoxic agents to act as methylome disruptors or remediators// MUTAGENESIS. -Vol. 26, nr. iss. 4 (2011), s.475-487
Weryfikacja:
Politechnika Gdańska

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