Abstract

A consortium of seven laboratories is proposed to focus the power of modern molecular analysis and cell technology on the processes of genetic change induced by environmental mutagenic agents. Each of these laboratories is experienced in developing and applying its own peculiar set of genetic, cellular and molecular techniques to the study of gene mutation in bacterial, yeast, rodent and human cells. These techniques include means to measure the amount, identify the structure and specify the position in DNA of a variety of mutagenic reaction products. The consortium is also capable of isolating and characterizing novel mutants in the process of mutagenesis and investigating the biochemical genetics of constitutive and inducible responses to premutagenic damage in such variant cells. The proposed relation would be particularly strong in its ability to identify, isolate and sequence genes related to the processes of mutagenesis and to study the role of the products of such genes in the molecular biology of cell responses to mutagenic agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES003926-05
Application #
3095920
Study Section
Environmental Health Sciences Review Committee (EHS)
Project Start
1985-09-27
Project End
1990-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Memisoglu, A; Samson, L (2000) Contribution of base excision repair, nucleotide excision repair, and DNA recombination to alkylation resistance of the fission yeast Schizosaccharomyces pombe. J Bacteriol 182:2104-12
Wyatt, M D; Samson, L D (2000) Influence of DNA structure on hypoxanthine and 1,N(6)-ethenoadenine removal by murine 3-methyladenine DNA glycosylase. Carcinogenesis 21:901-8
Opperman, T; Murli, S; Smith, B T et al. (1999) A model for a umuDC-dependent prokaryotic DNA damage checkpoint. Proc Natl Acad Sci U S A 96:9218-23
Hickman, M J; Samson, L D (1999) Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents. Proc Natl Acad Sci U S A 96:10764-9
Li-Sucholeiki, X C; Khrapko, K; Andre, P C et al. (1999) Applications of constant denaturant capillary electrophoresis/high-fidelity polymerase chain reaction to human genetic analysis. Electrophoresis 20:1224-32
Bennett, R A (1999) The Saccharomyces cerevisiae ETH1 gene, an inducible homolog of exonuclease III that provides resistance to DNA-damaging agents and limits spontaneous mutagenesis. Mol Cell Biol 19:1800-9
Ekstrom, P O; Borresen-Dale, A L; Qvist, H et al. (1999) Detection of low-frequency mutations in exon 8 of the TP53 gene by constant denaturant capillary electrophoresis (CDCE). Biotechniques 27:128-34
Glassner, B J; Posnick, L M; Samson, L D (1998) The influence of DNA glycosylases on spontaneous mutation. Mutat Res 400:33-44
Glassner, B J; Rasmussen, L J; Najarian, M T et al. (1998) Generation of a strong mutator phenotype in yeast by imbalanced base excision repair. Proc Natl Acad Sci U S A 95:9997-10002
Masuda, Y; Bennett, R A; Demple, B (1998) Dynamics of the interaction of human apurinic endonuclease (Ape1) with its substrate and product. J Biol Chem 273:30352-9

Showing the most recent 10 out of 77 publications