Variable effects of DNA-synthesis inhibitors upon DNA methylation in mammalian cells.

Abstract:

:Post-synthetic enzymatic hypermethylation of DNA was induced in hamster fibrosarcoma cells by the DNA synthesis inhibitors cytosine arabinoside, hydroxyurea and aphidicolin. This effect required direct inhibition of DNA polymerase alpha or reduction in deoxynucleotide pools and was not specific to a single cell type. At equivalently reduced levels of DNA synthesis, neither cycloheximide, actinomycin D nor serum deprivation affected DNA methylation in this way. The topoisomerase inhibitors nalidixic acid and novobiocin caused significant hypomethylation indicating that increased 5-mCyt content was not a necessary consequence of DNA synthesis inhibition. The induced hypermethylation occurred predominantly in that fraction of the DNA synthesized in the presence of inhibitor; was stable in the absence of drug; was most prominent in low molecular weight DNA representing sites of initiated but incomplete DNA synthesis; and occurred primarily within CpG dinucleotides, although other dinucleotides were overmethylated as well. Drug-induced CpG hypermethylation may be capable of silencing genes, an effect which may be relevant to the aberrantly expressed genes characteristic of neoplastic cells.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Nyce J,Liu L,Jones PA

doi

10.1093/nar/14.10.4353

subject

Has Abstract

pub_date

1986-05-27 00:00:00

pages

4353-67

issue

10

eissn

0305-1048

issn

1362-4962

journal_volume

14

pub_type

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