Identification and characterisation of human telomerase holoenzyme components

Funded Activity Summary

DNA is packaged into linear structures - chromosomes - that have two ends, called telomeres. When cells proliferate, their telomeres normally shorten slightly, and this ultimately limits the number of times cells can proliferate. This limitation is thought to contribute to ageing. Some tissues normally have a high rate of cell turnover (for example in the bone marrow which is constantly producing large numbers of new blood cells), and therefore a need for very extensive cellular proliferation. In these tissues, an enzyme called telomerase slows down (but does not completely prevent) the rate of telomere shortening by replacing some of the DNA that is lost as a result of proliferation. Telomerase is a complex enzyme with a number of subunits. In the past few years, it has started to become clear that inherited deficiencies of some of these subunits cause diseases in which cellular proliferation starts to fail at a young age. These patients typically die of bone marrow failure. In contrast to conditions where there is telomerase deficiency, the great majority of cancers have inappropriately high levels of telomerase activity which allow cancer cells to continue dividing without limit. Telomerase is therefore regarded as a very promising target for new cancer treatments. In view of the importance of telomerase to human health, it may seem very surprising that we do not yet know all of its subunits. The reason for this is that, even in telomerase-positive cancer cells, the amount of telomerase present is vanishingly small which has made it impossible so far to obtain sufficient quantities for even the most sensitive analytical techniques. We are using very large numbers of human cells grown in a bioreactor, and have devised a highly efficient method for purifying telomerase from them. We will analyse the purified telomerase by contemporary mass spectroscopy techniques, identify all of the subunits, and characterise their contribution to telomerase function.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $325,091.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Oncology and Carcinogenesis

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

ageing | aplastic anaemia | biochemistry and molecular biology | cancer and related disorders | cancer biology | cellular immortalisation | protein characterisation | telomerase | telomeres

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