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The Consequences of Whole Genome Duplications

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Whole genome duplications occur frequently during evolution, development and disease. The consequences of whole genome duplication are not well understood, but it has been speculated that the extra chromosome sets, extra centrosomes, and accompanying genomic instability might facilitate evolutionary adaptation. Our laboratory previously demonstrated that whole genome duplications triggered by cytokinesis failure could drive tumor development. Current estimates suggest that whole genome duplications occur in nearly 40% of human cancers at some point during tumor development. I will discuss recent work on the consequences of whole genome duplications in human somatic cells. First, I will discuss a mutagenesis mechanism that can occur if an intact chromosome is missegregated into abnormal nuclear structures called micronuclei. This results in extensive mutagenesis that is unusual because it is localized to one or a few chromosomes. Second, I will describe a new tumor suppressor signaling pathway that senses cytokinesis failure and prevents the proliferation of the resulting tetraploid cells.

This talk is part of the MRC LMB Seminar Series series.

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