BRCA1, PML and telomere maintenance

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Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects which contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear which are the most critical molecules contributing to this disease and thus which are the best targets for therapeutic intervention. In this proposal, we aim to study two molecules. The first is called BRCA1 and is particularly important in inherited susceptibility to breast cancer. The second is called PML and, although originally described as a leukaemia-associated gene, it has since been implicated in a number of cancers. Specifically, we aim to investigate the possibility that PML and BRCA1 work together to protect against cancer and that they do this by regulating the ends of chromosomes, that is, the telomeres.