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DNA Methyltransferases: A Novel Target for Prevention and Therapy
Cancer is the second leading cause of death in US. Despite the emergence of new, targeted agents, and the use of various therapeutic combinations, none of the available treatment options are curative in patients with advanced cancer. Epigenetic alterations are increasingly recognized as valuable tar...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013461/ https://www.ncbi.nlm.nih.gov/pubmed/24822169 http://dx.doi.org/10.3389/fonc.2014.00080 |
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author | Subramaniam, Dharmalingam Thombre, Ravi Dhar, Animesh Anant, Shrikant |
author_facet | Subramaniam, Dharmalingam Thombre, Ravi Dhar, Animesh Anant, Shrikant |
author_sort | Subramaniam, Dharmalingam |
collection | PubMed |
description | Cancer is the second leading cause of death in US. Despite the emergence of new, targeted agents, and the use of various therapeutic combinations, none of the available treatment options are curative in patients with advanced cancer. Epigenetic alterations are increasingly recognized as valuable targets for the development of cancer therapies. DNA methylation at the 5-position of cytosine, catalyzed by DNA methyltransferases (DNMTs), is the predominant epigenetic modification in mammals. DNMT1, the major enzyme responsible for maintenance of the DNA methylation pattern is located at the replication fork and methylates newly biosynthesized DNA. DNMT2 or TRDMT1, the smallest mammalian DNMT is believed to participate in the recognition of DNA damage, DNA recombination, and mutation repair. It is composed solely of the C-terminal domain, and does not possess the regulatory N-terminal region. The levels of DNMTs, especially those of DNMT3B, DNMT3A, and DNMT3L, are often increased in various cancer tissues and cell lines, which may partially account for the hypermethylation of promoter CpG-rich regions of tumor suppressor genes in a variety of malignancies. Moreover, it has been shown to function in self-renewal and maintenance of colon cancer stem cells and need to be studied in several cancers. Inhibition of DNMTs has demonstrated reduction in tumor formation in part through the increased expression of tumor suppressor genes. Hence, DNMTs can potentially be used as anti-cancer targets. Dietary phytochemicals also inhibit DNMTs and cancer stem cells; this represents a promising approach for the prevention and treatment of many cancers. |
format | Online Article Text |
id | pubmed-4013461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-40134612014-05-12 DNA Methyltransferases: A Novel Target for Prevention and Therapy Subramaniam, Dharmalingam Thombre, Ravi Dhar, Animesh Anant, Shrikant Front Oncol Oncology Cancer is the second leading cause of death in US. Despite the emergence of new, targeted agents, and the use of various therapeutic combinations, none of the available treatment options are curative in patients with advanced cancer. Epigenetic alterations are increasingly recognized as valuable targets for the development of cancer therapies. DNA methylation at the 5-position of cytosine, catalyzed by DNA methyltransferases (DNMTs), is the predominant epigenetic modification in mammals. DNMT1, the major enzyme responsible for maintenance of the DNA methylation pattern is located at the replication fork and methylates newly biosynthesized DNA. DNMT2 or TRDMT1, the smallest mammalian DNMT is believed to participate in the recognition of DNA damage, DNA recombination, and mutation repair. It is composed solely of the C-terminal domain, and does not possess the regulatory N-terminal region. The levels of DNMTs, especially those of DNMT3B, DNMT3A, and DNMT3L, are often increased in various cancer tissues and cell lines, which may partially account for the hypermethylation of promoter CpG-rich regions of tumor suppressor genes in a variety of malignancies. Moreover, it has been shown to function in self-renewal and maintenance of colon cancer stem cells and need to be studied in several cancers. Inhibition of DNMTs has demonstrated reduction in tumor formation in part through the increased expression of tumor suppressor genes. Hence, DNMTs can potentially be used as anti-cancer targets. Dietary phytochemicals also inhibit DNMTs and cancer stem cells; this represents a promising approach for the prevention and treatment of many cancers. Frontiers Media S.A. 2014-05-01 /pmc/articles/PMC4013461/ /pubmed/24822169 http://dx.doi.org/10.3389/fonc.2014.00080 Text en Copyright © 2014 Subramaniam, Thombre, Dhar and Anant. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Subramaniam, Dharmalingam Thombre, Ravi Dhar, Animesh Anant, Shrikant DNA Methyltransferases: A Novel Target for Prevention and Therapy |
title | DNA Methyltransferases: A Novel Target for Prevention and Therapy |
title_full | DNA Methyltransferases: A Novel Target for Prevention and Therapy |
title_fullStr | DNA Methyltransferases: A Novel Target for Prevention and Therapy |
title_full_unstemmed | DNA Methyltransferases: A Novel Target for Prevention and Therapy |
title_short | DNA Methyltransferases: A Novel Target for Prevention and Therapy |
title_sort | dna methyltransferases: a novel target for prevention and therapy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013461/ https://www.ncbi.nlm.nih.gov/pubmed/24822169 http://dx.doi.org/10.3389/fonc.2014.00080 |
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