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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046527-11
Application #
3189806
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1987-05-01
Project End
1992-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599