| Literature References | 1. LINGNER, J., HUGHES, T.R., SCHEVCHENKO, A., MANN, M., LUNDBLAD, V. AND
CECH, T.R.
Reverse transcriptase motifs in the catalytic subunit of telomerase.
SCIENCE 276 561-567 (2000).
2. LIU, J-P.
Telomerase: Not just Black and White, but Shades of Gray.
MOL.CELL.BIOL.RES.COMMUN. 3 129-135 (2000).
3. WANG, J., HANNON, G.J. AND BEACH, D.H.
Risky immortalization by telomerase.
NATURE 405 755-756 (2000).
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| Documentation | Telomerase is an enzyme that, in certain cells, maintains the physical ends
of chromosomes (telomeres) during replication. In somatic cells, replication
of the lagging strand requires the continual presence of an RNA primer
approximately 200 nucleotides upstream, which is complementary to the
template strand. Since there is a region of DNA less than 200 base pairs
from the end of the chromosome where this is not possible, the chromosome is
continually shortened. However, there is a surplus of repetitive DNA at the
ends, the telomeres, that protects against the erosion of gene-encoding DNA.
Telomerase is a ribonucleoprotein (RNP) that synthesises the telomeric DNA
repeats. The telomerase RNA subunit provides the template for synthesis of
these repeats. There are 2 protein components of the RNP: the catalytic
subunit is known as telomerase reverse transcriptase (TERT). The reverse
transcriptase domain is located in the C-terminal region of the TERT
polypeptide and single amino acid substitutions in this region lead to
telomere shortening and senescence [1].
Telomerase is not normally expressed in somatic cells and it has been
suggested that exogenous TERT may extend the lifespan of, or even
immortalise, the cell. However, recent studies have shown that telomerase
activity can be induced by a number of oncogenes [2]. Conversely, the
oncogene c-myc can be activated in human TERT immortalised cells [3].
TELOMERASERT is a 4-element fingerprint that provides a signature for the
telomere reverse transcriptase. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from conserved regions
spanning the C-terminal half of the alignment. Two iterations on SPTR37_10f
were required to reach convergence, at which point a true set comprising 9
sequences was identified.
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