Investigations into genetically controlled structural heterogeneity of the human DNA methyltransferases 1, 2 and 3B with particular emphasis on relevance to the development of non-Hodgkin's lymphoma

[Truncated] DNA methylation is a sequence specific, post-synthetic modification which involves the enzyme catalysed transfer of a methyl group from a donor, S-adenosylmethionine, to either the 5th carbon position of cytosine or the 6th amino group of adenine in polymeric DNA. The latter reaction occurs predominately in prokaryotes and lower eukaryotes whereas cytosine-CS methylation is the most frequent modification of mammalian DNA. The subject of this thesis is cytosine-CS methylation.
Genomic de nova methylation of cytosine residues, such as those within the myogenic gene Myf-3, is a characteristic feature of many different types of malignant cells, including those of lymphoid origin. Thus far, however, it is unclear, which, if any, of the human DNA (cytosine-5) methyltransferases (DNMTs) are critically involved in establishing the abnormal hypermethylation profile associated with malignancy. This thesis aimed to identify the DNA methylating enzyme or enzymes which may play a role in the early stages of non-Hodgkin's lymphoma by finding disturbances in the frequency of phenotypes or alleles encoding each of these enzymes in DNA from these patients.