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Mechanisms of genome instability induced by RNA splicing defects

Peter Stirling

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Canadian Institutes of Health Research (CIHR)
Cancer is a disease caused by mutations in normal genes. Due to so-called 'genome instability', most cancers have an increased frequency of mutations compared to normal cells. The yeast model system has proven to be a valuable tool in defining mechanisms of genome maintenance. My research program will define the causes and consequences of genome instability in yeast as a means to understand how cancers develop and how they can be selectively targeted with therapies. Specifically, we have shown that genes involved in a fundamental activity called RNA splicing were unexpectedly important for genome maintenance. Focusing on RNA splicing factors that have been linked to genome maintenance in both yeast and human cells, we will define how genome instability occurs when these splicing functions are disrupted. Some of the human counterparts of these splicing factors are frequently mutated in leukemia, breast, and other cancers. Therefore, another aim of the research will be to specifically test the consequences of these tumour-associated mutations on splicing function and genome maintenance.The work is of fundamental importance to defining the biological networks that normally protect our cells from genome instability and to understanding potential causes of genome instability in human disease.

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