Genetic assays and strains using human TP53

Details Genetic assays and strains using human TP53 Genetic assays and strains using human TP53

1996-05-01

1998-11-03

Carlson, Karen Cochrane

Chemistry: molecular biology and microbiology

Micro-organism, per se ; compositions thereof; proces of...

Fungi

4353201, 536 231, 536 234, C12N 114, C07H 1700

Patent

active

058307516

ABSTRACT:
Yeast strains carrying a human wild-type TP53 are employed to select for mutations. The types of mutations can be analyzed genetically as recessive or dominant-negative. The mutational spectrum of dominant-negative TP53 mutants selected in yeast correlates tightly with TP53 mutations found in human cancers. Thus the use of such yeast assays is validated for studying the effects of various agents on human TP53, one of the most important and ubiquitous of human cancer genes. Assays, kits, and constructs are provide which use yeast as a genetic system for making and studying human TP53 mutations. Such assays can be used to develop therapeutic agents, to study putative carcinogens, and to identify other cellular components which interact with p53 and abrogate its activity.

REFERENCES:
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Saluz et al., "Approaches to Chracterize Protein-DNA Interactions In Vivo", Critical Review in Eukaryotic Gene Expression 3(1):1-29 (1993).
Brachmann, et al., "Dominant-negative p53 Mutations Selected in Yeast Hit Cancer Hot Spots", Proc. Natl. Acad. Sci. USA, vol. 93, pp. 4091-4095 (Apr. 1995).
Cho, Y. et al., "Crystal structure of p53 tumor suppressor-DNA complex: Understanding Tumorigenic mutations" Science 15 Jul. 1994. vol. 265 pp. 346-355.
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Lasky, T. et al. "p53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers" Environmental Health Perspectives Dec. 1996 vol. 104, No. 12. pp. 1324-1331.
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