PMID: 9524758Jan 1, 1997Paper

Genetic control of telomerase and replicative senescence in human and rodent cells

Ciba Foundation Symposium
R F Newbold

Abstract

The ribonucleoprotein telomerase is detectable in most human cancer cells and immortalized cells but is absent or inactive in the vast majority of normal counterparts. Repression of telomerase activity in human somatic cells, which leads to telomere shortening and replicative senescence, may have evolved as a protective mechanism against immortalization, unfettered clonal evolution and cancer. Rodent cells in culture are far more susceptible to immortalization and malignant progression than human cells. This can be explained by our observation that normal diploid rodent (hamster) fibroblasts possess active telomerase throughout their proliferative life span, and therefore they do not require a telomerase activation step during immortalization. Monochromosome transfer techniques have enabled us to identify powerful telomerase repressive activity specifically associated with the introduction of a single copy of human chromosome 3 into human carcinoma cells. Fine-structure deletion analysis of non-repressed hybrids has permitted us to map the position of the candidate telomerase repressor gene to 3p21.1-3p21.3. A strategy for isolating the gene has been developed involving a combination of fine-structure deletion mapping and funct...Continue Reading

Citations

Jun 6, 2018·Frontiers in Molecular Neuroscience·Meng-Ying LiuQi-Gang Zhou

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