Structure of the rat p53 tumor suppressor gene
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Updated: Nov 7, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
1Pacific Northwest Laboratory, Richland, WA 99352.
Abstract:
Aberration within the p53 tumor suppressor gene is the most frequently identified genetic damage in human cancer. Regulatory functions proposed for the p53 protein include modulation of the cell cycle, cellular differentiation, signal transduction, and gene expression. Additionally, the p53 gene product may guard the genome against incorporation of damaged DNA. To facilitate study of its role in carcinogenesis using a common animal model, we determined the structure of the rat p53 gene. We identified 18 splice sites and defined 25 bases of the intervening sequences adjacent to these sites. We also discovered an allelic polymorphism that occurs within intron 5 of the gene. The rat gene approximates the mouse ortholog. It is 12 kb in length with the non-coding exon 1 separated from exon 2 by 6.2 kb of intervening sequence. The location and size of all rat gene introns approximate those of the mouse. Whereas the mouse and human genes each contain 11 exons, the rat p53 gene is composed of only 10. No intervening sequence occurs between the region of the rat gene corresponding to exons 6 and 7 of the mouse and human p53 genes. This implies intron 6 may be functionally insignificant for species in which it is retained. To extrapolate to p53 involvement in human tumorigenesis, we suggest that mutational events within intron 6 may not be of pathological significance unless splicing is hindered.
Insights
The rat p53 tumor suppressor gene structure was determined, revealing 10 exons and significant differences from mouse and human genes. Intron 6 may be functionally insignificant in rats, impacting cancer research insights.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- p53 tumor suppressor gene aberrations are common in human cancers.
- p53 protein regulates cell cycle, differentiation, signal transduction, and gene expression.
- p53 may protect the genome from damaged DNA integration.
Purpose of the Study:
- To determine the structure of the rat p53 gene for cancer research.
- To compare the rat p53 gene structure with mouse and human orthologs.
Main Methods:
- Gene structure determination in a rat model.
- Identification of splice sites and intervening sequences.
- Analysis of allelic polymorphism within intron 5.
Main Results:
- The rat p53 gene has 10 exons, differing from the 11 exons in mouse and human genes.
- Identified 18 splice sites and defined intervening sequences.
- Discovered an allelic polymorphism in intron 5.
- Rat p53 gene structure closely approximates the mouse ortholog.
- No intervening sequence between rat exons corresponding to mouse/human exons 6 and 7.
Conclusions:
- Rat p53 gene structure provides a model for studying p53's role in carcinogenesis.
- Intron 6's lack of intervening sequence suggests potential functional insignificance in rats.
- Mutations in intron 6 may not be pathologically significant unless they disrupt splicing.
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