Journal
EMBO JOURNAL
Volume 28, Issue 17, Pages 2532-2540Publisher
WILEY
DOI: 10.1038/emboj.2009.172
Keywords
cancer; dyskeratosis; mutations; telomerase
Categories
Funding
- Canadian Institutes of Health Research [MOP38075, GMH79042]
- National Cancer Institute of Canada
Ask authors/readers for more resources
The telomeres of most eukaryotes are characterized by guanine-rich repeats synthesized by the reverse transcriptase telomerase. Complete loss of telomerase is tolerated for several generations in most species, but modestly reduced telomerase levels in human beings are implicated in bone marrow failure, pulmonary fibrosis and a spectrum of other diseases including cancer. Differences in telomerase deficiency phenotypes between species most likely reflect a tumour suppressor function of telomeres in long-lived mammals that does not exist as such in short-lived organisms. Another puzzle provided by current observations is that family members with the same genetic defect, haplo-insufficiency for one of the telomerase genes, can present with widely different diseases. Here, the crucial role of telomeres and telomerase in human (stem cell) biology is discussed from a Darwinian perspective. It is proposed that the variable phenotype and penetrance of heritable human telomerase deficiencies result from additional environmental, genetic and stochastic factors or combinations thereof. The EMBO Journal (2009) 28, 2532-2540. doi: 10.1038/emboj.2009.172; Published online 23 July 2009 Subject Categories: molecular biology of disease
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available