DNA methylation is an important epigenetic mechanism of transcriptional control, which plays an essential role in maintaining cellular function. Role of one-
carbon transfer agents/methyl donors namely
folate,
choline and
methionine in DNA methylation has been the subject of extensive investigation. The methylation pattern of
DNA is established during embryogenesis by
DNA methyltransferase 3 (dnmt3) and is subsequently maintained by maintenance methylation activity of the
enzyme DNA methyltransferase 1 (dnmt1). Ionizing radiation is known to extensively damage the
DNA. Sufficient dietary availability of methyl donors is known to contribute towards one-
carbon transfer mediated repair of damaged
DNA where
folate is involved in
nucleotide base synthesis. In the present study, modification in activities of dnmt1 and dnmt3 by methyl donor
starvation followed by gamma-irradiation was observed. Assays were based on the catalytic transfer of (3)H-methyl groups from
S-adenosyl-L: -methionine to
a DNA substrate. Experiments showed a dose and methyl donors
starvation dependent attenuation in dnmt1 activity. Attenuation of dnmt1 activity was most significant for diet deprived of all the three-methyl donors. No significant change in nuclear or cytoplasmic dnmt3 activity was observed when either or all the three possible source of dietary methyl group supply were removed. Ionizing radiation and methyl donor deficiency were observed to act synergistically towards inhibiting dnmt1 activity. Present results suggested possibility of interaction among
folate,
methionine and
choline deficiency to potentiate symptoms of ionizing radiation stress. These enzymatic modifications might contribute to altered DNA methylation after chronic feeding of methyl donor free diets followed by gamma irradiation. These results suggested that dietary availability of methyl donors and gamma-radiation stress might significantly alter the dnmt1 profile.