Regulation of topoisomerase ii during the cell division cycle

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Project objective

Topoisomerase II is a nuclear enzyme required for cell division in all eukaryotes. In human cells, two distinct isozymes of topoisomerase II are expressed, termed a (170 kDa form) and D (180 kDa form). Both isozymes are known to be phosphoproteins in vivo. Topoisomerase IIa and B are also targets for inhibition by a range of the most commonly used anticancer drugs. We propose to investigate the functional significance of changes in the phosphorylation status of human topoisomerase IIa protein. These analyses will be conducted in two different systems: the budding yeast S. cerevisiae and human cell lines in tissue culture. Human topoisomerase IIa protein purified from yeast cells will be studied in comparison with mutant topoisomerase IIa proteins containing single amino acid substitutions eliminating key phosphoacceptor residues identified recently in the host laboratory. The mutated cDNAs encoding these phosphorylation site mutants will be overexpressed in human cells and dominant negative effects on cell cycle progression and faithful chromosome segregation analysed.

Original text from CORDIS.

Participants

• Aristotle University of Thessaloniki · ThessalonikiCoordinatorGreece

Links

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