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Modulation of DNA Methylation for the Treatment and Prevention of Cancer

  • David S. Schrump
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Alterations in chromatin structure represent early and critical events that perturb gene expression during multistep carcinogenesis (1). The nucleosome—the basic structure of chromatin is composed of 146 basepairs of DNA coiled around an octamer of core histones (H2A, H2B, H3, and H4); nucleosomes are separated by variable lengths of linker DNA bound to histone H1 . In association with additional proteins, nucleosomes are assembled into higher order chromatin (2).The modulation of histone proteins by acetylation, phosphorylation, or methylation influences the nature and specificity of DNA-histone interactions, thus influencing gene activity (2–4). For example, deacetylation of core histone proteins by histone deacetylases (HDACs) increases DNA-histone interactions, resulting in chromatin compaction and repression of transcription, whereas acetylation of histones by histone acetyl transferases (HATs) diminishes DNA-histone binding, resulting in chromatin relaxation and enhanced gene expression (5, 6).

Keywords

Proliferate Cell Nuclear Antigen Malignant Pleural Mesothelioma Malignant Mesothelioma Normal Human Bronchial Epithelial DNMT Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 2004

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  • David S. Schrump

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