DNA methylation and cancer
Yoshikawa, H.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 34(2): 145-149
2007
ISSN/ISBN: 0385-0684 PMID: 17301518 Document Number: 610232
Tumor suppressor genes can be silenced by DNA methylation during cancer development. Aberrant DNA methylation is closely associated with histone deacetylases and histone methyltransferases that can modify histone amino-terminal lysines and develop specific histone codes, resulting in inactive chromatin formation. These processes change epigenetic information that builds up abnormal chromatin structure, and creates the unique features of cancer cells. It is well known that thousands of genes are deregulated in cancer cells. Epigenetic alterations involving aberrant DNA methylation is a possible mechanism that can explain the genome-wide abnormality of gene expression. The mechanism responsible for the aberrant DNA methylation is unclear now, however it seems that de novo DNA methyltransferases (DNMTs) play an important role in the process. DNMT3 A and DNMT3B are thought to be de novo DNMTs in human. A nucleoside analogue of cytidine induces demethylation of DNA in cancer cells by inhibiting the function of DNMTs. It is significant to elucidate precise mechanisms of aberrant DNA methylation and develop small molecules that can inhibit methylation.