Title: Mechanisms of telomere cap function DNA within each cell is packaged into chromosomes, the ends of which are called telomeres. The DNA in telomeres consists of 6 letters of the genetic code, TTAGGG, repeated hundreds or thousands of times. A number of proteins, including some that have not yet been identified, bind to this DNA and form a cap structure to protect the chromosome ends. Telomeres need to be able to serve a number of specialised functions, including protection against enzymes ....Title: Mechanisms of telomere cap function DNA within each cell is packaged into chromosomes, the ends of which are called telomeres. The DNA in telomeres consists of 6 letters of the genetic code, TTAGGG, repeated hundreds or thousands of times. A number of proteins, including some that have not yet been identified, bind to this DNA and form a cap structure to protect the chromosome ends. Telomeres need to be able to serve a number of specialised functions, including protection against enzymes that degrade DNA ends, and preventing chromosome ends from sticking to each other, while allowing access for DNA copying enzymes when the cell is preparing to divide into two. In some inherited conditions, the telomeres fail to perform these functions efficiently, leading to cellular dysfunction, premature ageing of cells, and ultimately disease. In some types of cells, especially cancer cells, the telomeres also permit the access of molecular machinery that lengthens the telomeres. There are at least two types of lengthening processes, one of which is a complex enzyme called telomerase, and the other an incompletely characterised process that we discovered and named Alternative Lengthening of Telomeres (ALT). In some circumstances, the telomeres of cancer cells appear to be able to discriminate between telomerase and ALT, and to allow one mechanism to operate but not the other. We will analyse how telomeres perform their capping functions, and will determine the differences between normal and cancer cells in this regard. This will lay the groundwork for efforts to develop new forms of cancer treatment that act by preventing cancer cells from lengthening their telomeres.Read moreRead less
Molecular Targeting To Telomerase And Cancer Cell Immortality By A Novel Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$430,812.00
Summary
Infinite growth of cancer cells is a hallmark of cancer. Telomerase is required for cancer cell immortality. Inhibition of telomerase may thus offer an opportunity to stop cancer cells. We have identified an inhibitor of telomerase. This project will study the mechanisms of action of the novel inhibitor, investigating how to control cancer cell immortality as a baseline for more applied anti-cancer therapeutic studies.
Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.