The long range objectives of this research are to establish the role of mispairing in mutagenesis and to determine the mechanism for the environmental enhancement of substitution mutations. The importance of this project stems from the role of mutations in gene variation, both normal and pathogenic, and from a recognition that many mutagenic and carcinogenic substances are a byproduct of our growing industrial technology. The use of in vitro replication studies utilizing a reconstituted replication apparatus offers distinct advantages for this project. The well defined proteins and template-primers allow careful dissection of the chemistry involved in mutagenesis and the effect on this chemistry of environmental agents. The following investigations are proposed: 1) Determination of the role of the proteins of the replication apparatus on the fidelity of replication. 2) Determination of which particular chemical modifications of a base induce a mutation. 3) Determination of the role of minor tautomeric forms and syn isomers of the nucleic acid residues in mutagenesis.
| Reid, R; Mar, E C; Huang, E S et al. (1988) Insertion and extension of acyclic, dideoxy, and ara nucleotides by herpesviridae, human alpha and human beta polymerases. A unique inhibition mechanism for 9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate. J Biol Chem 263:3898-904 |
| Huff, A C; Topal, M D (1987) DNA damage at thymine N-3 abolishes base-pairing capacity during DNA synthesis. J Biol Chem 262:12843-50 |
| Topal, M D; Eadie, J S; Conrad, M (1986) O6-methylguanine mutation and repair is nonuniform. Selection for DNA most interactive with O6-methylguanine. J Biol Chem 261:9879-85 |
| Conrad, M; Topal, M D (1986) Induction of deletion and insertion mutations by 9-aminoacridine. An in vitro model. J Biol Chem 261:16226-32 |
| Topal, M D (1985) Mutagenesis by incorporation of alkylated nucleotides. Basic Life Sci 31:339-51 |
