Project Title:

Investigating the role of Topoisomerase II alpha during mitosis

Project Summary:

My project is mainly focused on the role of Topoisomerases II in human chromosome condensation. I am studying the two isoforms, alpha and beta, in their interaction with DNA duplexes for catenation/decatenation, and their relief of superhelical tension. Depletion of Topoisomerases II has been thoroughly performed, as many chemotherapy drugs disturb the proteins. Depletion of Topoisomerase II alpha, in particular, leads to many phenotypes - impaired condensation of mitotic chromosomes, failure to decatenate sister chromatids, chromatin bridges and lagging chromosomes in anaphase - that illustrate its varied roles. One of the phenotypes - the trapped-arm phenotype, characterised by chromosomes loops escaping the congressed chromosomes and appearing trapped at centrosomes - is of particular interest to me. This phenotype could be explaining Topoisomerase II alpha’s role as a chromosomal scaffold. Depletion of the Topoisomerases II also perturbs proteins interacting with Topoisomerases II, such as TOPBP1. Studying the phenotypes arising from the depletions, I am trying to understand how these proteins all interact, both on chromatin and at centrosomes, and how important they are in chromosome condensation.