Telomerase, whose core components are a
reverse transcriptase (TERT) and an integral
RNA (
TERC) maintains telomere ends. In somatic cells in the absence of
telomerase telomeres get shorter leading to replicative cell senescence. In
cancer cells abundant
telomerase is present and cells do not senesce. Hence levels of
telomerase may be crucial in regulating senescence and the transition to the neoplastic state. Heterozygous
TERC mutations in man have been shown to underlie the rare inherited skin and
bone marrow failure condition
dyskeratosis congenita and a number of patients initially classified as
idiopathic aplastic anemia have also been found to be mutated in one allele of the
TERC gene. Families in which
TERC mutations are segregating show disease anticipation, the severity of the disease increasing in successive generations due to decreasing telomere length. These data, along with biochemical analysis of mutated
Terc and studies of
Terc deficient mice show that in man and mouse haploinsufficiency for
TERC leads to inability to correctly maintain telomeres, and highlights the importance of finely controlled
telomerase levels in striking a balance between the processes of aging and
cancer. Here we review several scenarios in which
telomerase levels are disturbed, in human diseases or following genetic manipulation in mice.