The mechanisms controlling cell growth are often disrupted in cancers. Here we will investigate a fundamental mechanism that ensures that every daughter cells receives identical copies of DNA. This control mechanism also appears to have a key role in protecting the cells that continuously repopulate the epidermal layer ofthe skin that are target for ultraviolet radiation induced mutation that lead to skin cancers. This mechanism is inoperative in cells derived from skin cancers, indicating that ....The mechanisms controlling cell growth are often disrupted in cancers. Here we will investigate a fundamental mechanism that ensures that every daughter cells receives identical copies of DNA. This control mechanism also appears to have a key role in protecting the cells that continuously repopulate the epidermal layer ofthe skin that are target for ultraviolet radiation induced mutation that lead to skin cancers. This mechanism is inoperative in cells derived from skin cancers, indicating that mutation of components of this mechanism must have occurred. These mutations, and the loss of this normally protective control mechanism are likely to contribute to either an increased risk of skin cancer, or to the increased malignant spread of the diseases.Read moreRead less
G2 Phase Cdk2/cyclin A Co-ordinates Multiple Pathways In G2/M Progression
Funder
National Health and Medical Research Council
Funding Amount
$302,036.00
Summary
Cell growth is a tightly regulated process that ensures the exact duplication of the entire genomic DNA followed by division of the cell into two identical daughter cells. If this strict ordering of events is in any way disrupted, the resultant daughter cells would have a different complement of DNA from their parent cell, essentially mutant cells. The cell has established a mechanism to ensure the correct ordering of these crucial events, known as the cell cycle, and mechanisms that can respond ....Cell growth is a tightly regulated process that ensures the exact duplication of the entire genomic DNA followed by division of the cell into two identical daughter cells. If this strict ordering of events is in any way disrupted, the resultant daughter cells would have a different complement of DNA from their parent cell, essentially mutant cells. The cell has established a mechanism to ensure the correct ordering of these crucial events, known as the cell cycle, and mechanisms that can respond to disruptions in this ordering and halt the normal cell cycle mechanism until the fault is rectified. These are the checkpoint controls. Checkpoint controls also respond to environmental stresses such as toxins that can damage the DNA to produce mutations. In diseases such as cancer, these checkpoint mechanisms are often faulty, allowing the cells to accumulate DNA mutations which can ultimately result in the cells becoming the aggresive, malignant tumours associated with the worst forms of this disease. Thus a detailed understanding of the cellular mechanisms involved in normal cell cycle and checkpoint control is important in not only defining the causes of these diseases at a molecular level, but may ultimately provide molecular targets for drugs that specifically destroy cancer cells by targeting the faulty checkpoint control. This proposal will investigate one component of the cell cycle mechanism, cdk2-cyclin A, which also has a major role in checkpoint control, to determine its exact role in both these important cellular growth controls.Read moreRead less
The Role Of Centromere Proteins In Centromere Assembly, Chromosome Instability, And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$687,750.00
Summary
Our genetic information are organised into compact structures known as chromosomes in our cells. Each human cell has 46 chromosomes. Excess or insufficient copies of these chromosomes will cause genetic imbalance that often results in serious clinical problems such as Down syndrome, cancer, embryonic death, and a host of other syndromes. The study of the process of how the exact number of chromosomes is distributed amongst daughter cells when cells divide is therefore an important area of resear ....Our genetic information are organised into compact structures known as chromosomes in our cells. Each human cell has 46 chromosomes. Excess or insufficient copies of these chromosomes will cause genetic imbalance that often results in serious clinical problems such as Down syndrome, cancer, embryonic death, and a host of other syndromes. The study of the process of how the exact number of chromosomes is distributed amongst daughter cells when cells divide is therefore an important area of research. Our laboratory has focused research on a key structure of the chromosome known as the centromere that determines how this process is controlled. The present project aims to study the properties of the centromere in detail using the technique of targeted gene mutation in mice. In these mice, the functions of individual genes that make specific centromere proteins are destroyed or modified through a precisely controlled mutation process. The effects such mutations have on the development of the animals and on chromosome division can then be analysed in great detail. The outcome will be a significant increase in our understanding of the functions of the different centromere proteins, an understanding that is key to the further advancement of our knowledge on the aetiology of some of the most frequently seen disease conditions in humans, including cancer.Read moreRead less