Inhibition of DNA replication, DNA repair synthesis, and DNA polymerases. cap alpha. and delta by butylphenyl deoxyguanosine triphosphate
Semiconservative DNA replication in growing mammalian cells and ultraviolet (UV)-induced DNA repair synthesis in nongrowing mammalian cells are mediated by one or both of the aphidicolin-sensitive DNA polymerases, ..cap alpha.. and/or delta. They have studied the inhibition of replication and repair synthesis in permeable human cells by N/sup 2/ (p-n-butylphenyl)-2'-deoxyguanosine-5'-triphosphate (BuPh dGTP), an agent which inhibits polymerase ..cap alpha.. strongly and polymerase delta weakly. Both processes are inhibited by BuPh-dGTP in competition with dGTP. The K/sub i/'s are, for replication, 2-3 ..mu..M and, for repair synthesis, 3-4 ..mu..M, consistent with the involvement of the same DNA polymerase in both processes. Inhibition of isolated human polymerase ..cap alpha.. by BuPh-dGTP is also competitive with dGTP, but the K/sub i/ is approximately 10 nM, several hundred-fold lower than the K/sub i/'s of replication and repair synthesis. Isolated polymerase delta is inhibited by BuPh-dGTP at doses similar to those which inhibit replication and repair synthesis, however, attempts to determine the K/sub i/ of polymerase delta were hampered by the finding that the dependence of delta activity on deoxyribunucleotide concentration is parabolic at low doses. This behavior differs from the behavior of polymerase ..cap alpha.. and of cellular DNA replication and repair synthesis, all of which show a simple, hyperbolic relationship between activity and deoxyribonucleotide concentration. Thus, inhibition of DNA replication and UV induced DNA repair synthesis by BuPh dGTP is quantitatively similar to DNA polymerase delta, but some other characteristics of the cellular processes are more similar to those of polymerase ..cap alpha...
- Research Organization:
- Washington Univ. School of Medicine, St. Louis, MO
- OSTI ID:
- 6064785
- Report Number(s):
- CONF-870644-; TRN: 87-037489
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
- Country of Publication:
- United States
- Language:
- English
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ANIMAL CELLS
DNA REPLICATION
GENETIC RADIATION EFFECTS
DNA POLYMERASES
ENZYME ACTIVITY
ENZYME INHIBITORS
BIOLOGICAL FUNCTIONS
DNA REPAIR
GUANYLIC ACID
INHIBITION
MAN
ULTRAVIOLET RADIATION
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
ELECTROMAGNETIC RADIATION
ENZYMES
FUNCTIONS
GENETIC EFFECTS
MAMMALS
NUCLEIC ACID REPLICATION
NUCLEOTIDES
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PRIMATES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
TRANSFERASES
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture