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Chromatin Remodeling, Cancer and Chemotherapy

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Abstract:

DNA in eukaryotic nucleus is highly condensed with histone proteins as nucleosomes. Three dimensional arrangements of nucleosomes give rise to the formation of chromatin. Extensive studies in the recent years have highlighted that the structure of chromatin plays a critical role in gene expression. Post translational modifications (such as acetylation, deacetylation, methylation and phosphorylation etc.) of tails of histones may occur with the help of various histone modifier proteins which may lead to architectural changes of nucleosomes and chromatin remodeling. Chromatin remodeling may finally enhance or repress gene transcriptions. The neoplastic cells selectively take the advantages of histone modifications for the cell proliferation, differentiation and evasion of apoptosis. There are enough experimental and clinical evidences that various histone modifiers are linked with many human malignancies. The thorough knowledge of manipulation of histone modifiers by cancer cells may help us to design newer anti-neoplastic drugs in future. There is considerable interest in histone deactylase inhibitors as antineoplastic agents and various clinical trials are in progress. This article reviews a general overview of chromatin remodeling proteins, their role in carcinogenesis and the future potential of the histone deacetylase inhibitors in cancer chemotherapy

Keywords: Histone modifiers; carcinogenesis; chemotherapy; chromatin; nucleosome

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986706778521850

Affiliations: Department of Cytology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Publication date: October 1, 2006

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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