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Research Paper
DNA Hypermethylation and Partial Gene Silencing of Human Thymine-DNA Glycosylase in Multiple Myeloma Cell Lines
Benjamin Peng, Elaine M. Hurt, David R. Hodge, Suneetha B. Thomas and William L. Farrar
volume 1 | issue 3
july/august/september 2006Pages: 138 - 145
This is an open-access article
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Multiple myeloma (MM) has prominent features of karyotypic instability at the earliest
stage, leading to extreme genetic abnormalities as the disease progresses. These
successive genetic alterations can be attributed, in part, to defects in DNA repair
pathways. A possible mechanism of dysregulation of the DNA repair pathway is
epigenetic gene silencing. Therefore, we sought to determine the methylation status of
enzymes involved in the base excision repair pathway in multiple myeloma cell lines.
Here, we report the aberrant DNA methylation of TDG, one of the enzymes involved in
base excision repair of damaged DNA, in several multiple myeloma cell lines but not in
normal human plasma cells. DNA hypermethylation of TDG in the MM cell lines leads
to lower gene expression levels that results in less efficient DNA repair activity in
response to hydrogen peroxide-induced DNA damage. Expression of exogenous TDG
can functionally compensate for lower repair activities of damaged DNA in the KAS-6/1
myeloma cell line, which has extensive DNA hypermethylation of the TDG promoter.
Hypermethylation of DNA damage repair genes in MM cell lines may provide an
explanation for the frequent genomic instability, as well as point mutations, that are
encountered in MM.
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.