Perturbation of maintenance and de novo DNA methylation in vitro by UVB (280-340 nm)-induced pyrimidine photodimers

Journal Article · Sun Sep 01 00:00:00 EDT 1985 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.82.18.6055· OSTI ID:6429098

Becker, F F; Holton, P; Ruchirawat, M; Lapeyre, J N

The effect of pyrimidine photodimers on transmethylation reactions catalyzed by a highly purified rat liver DNA (cytosine-5-)-methyltransferase (EC 2.1.1.37) that exhibits maintenance and de novo methylation activities was studied in vitro, using the viral substrates M13 mp9 replicative form (RF) DNA and the hemimethylated analog formed from primed synthesis of phage DNA in the presence of 2'-deoxy-5-methylcytidine 5'-triphosphate. These DNAs were irradiated with UVB (280-340 nm) at 900-3600 J/m/sup 2/ in the presence of the triplet-state sensitizers acetone or 3-dimethylaminopropiophenone. Under these conditions of irradiation, which approximate solar UV, pyrimidine cyclobutane photodimers were introduced without producing any evidence of single-strand breaks or alkali-sensitive sites. The methylation of irradiated templates by DNA methyltransferase was inhibited in an approximately linear fashion as a function of increasing UVB dose. This inhibition was correlated with the number of lethal photoproducts detected by the simultaneous measurement of the surviving fraction of infectious phage DNA. For approximately the same number of pyrimidine cyclobutane photoproducts introduced, de novo methylation activity was approx. =2-fold more sensitive than the maintenance mode of methylation. The ability of these putatively carcinogenic, pyrimidine photoproducts to inhibit DNA methylation suggests a common mechanism of action with several chemical carcinogens that are known to modify bases.

• Research Organization: M. D. Anderson Hospital and Tumor Institute, Houston, TX
• OSTI ID: 6429098
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 82:18
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DNA
BIOLOGICAL RADIATION EFFECTS
METHYLATION
INHIBITION
PYRIMIDINE DIMERS
RADIOINDUCTION
FAR ULTRAVIOLET RADIATION
IN VITRO
TRANSFERASES
TRITIUM COMPOUNDS
BIOLOGICAL EFFECTS
CHEMICAL REACTIONS
ELECTROMAGNETIC RADIATION
ENZYMES
LABELLED COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RADIATION EFFECTS
RADIATIONS
ULTRAVIOLET RADIATION
560111* - Radiation Effects on Biochemicals- In Vitro- (-1987)