CDK4 Activity In S/G2 Phases Influences Mitotic Fidelity
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The ultraviolet radiation component of the sunlight is a major environmental factor in the development of skin cancers, including melanomas. Over the past 10 years a genetic factors have also been identified that predispose towards developing melanoma, although the connection between ultraviolet radiation and the genetic factors has remained elusive. In this study we will investigate a cellular mechanism that potentially explains the link between sunlight exposure and one of the genetic risk fac ....The ultraviolet radiation component of the sunlight is a major environmental factor in the development of skin cancers, including melanomas. Over the past 10 years a genetic factors have also been identified that predispose towards developing melanoma, although the connection between ultraviolet radiation and the genetic factors has remained elusive. In this study we will investigate a cellular mechanism that potentially explains the link between sunlight exposure and one of the genetic risk factors. We will also examine whether targeting the pathway this genetic factor normally operates in can deliver increased therapeutic benefit to an existing chemotherapeutic treatment.Read moreRead less
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
The mechanisms controlling cell growth are often disrupted in cancers. We have identified on such growth control mechanism. When normal body cells are treated with a particular family of drugs known as histone deacetylase inhibitors, they react by stopping proliferating, but will resume normal growth when the drug is removed. However, we have found that similarly treated tumour cells are killed by these drugs. The difference between the normal and tumour cells is the functionality of a particula ....The mechanisms controlling cell growth are often disrupted in cancers. We have identified on such growth control mechanism. When normal body cells are treated with a particular family of drugs known as histone deacetylase inhibitors, they react by stopping proliferating, but will resume normal growth when the drug is removed. However, we have found that similarly treated tumour cells are killed by these drugs. The difference between the normal and tumour cells is the functionality of a particular growth control. The identification of how this growth control mechanism operates in normal cells, and defining the defect in tumour cells has the potential to identify new targets for more specific and potent anti-cancer drugs. The increased specificity, i.e. destruction of only the tumour cells while have little or no effect on the surround normal body tissue, would be extremely beneficial as one of the drawbacks to conventional anti-cancer treatments is their unwanted normal tissue toxicities. This is cause of the many debilitating side effects associated with chemo and radiotherapy which can limit the clinical effectiveness of these treatments.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
Role Of Condensin In Chromosome Organisation And Regulation
Funder
National Health and Medical Research Council
Funding Amount
$589,425.00
Summary
When a cell divides, its hereditary material (DNA) must be copied and equally segregated into each daughter cell. Our DNA is organised into a number of long units known as chromosomes. In order for our genetic material to be faithfully segregated into two daughter cells, the chromosomes must compact nearly 10,000 fold. A key component is condensin and we aim to find out how condensin directs the organisation and compaction of the mammalian chromosome.