Charbin, AA; (2012) The role of condensin in chromosome resolution. Doctoral thesis , UCL (University College London).

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Abstract

The condensin complex is a key determinant of mitotic chromosome architecture. In addition to its role in mitotic chromosome compaction, condensin is required for resolution of sister chromatid linkages during chromosome segregation in anaphase. How condensin resolves sister chromatids, and the nature of the chromosome bridges that are characteristic of cells harboring defective condensin, have remained topics of debate. Inactivation of topoisomerase II, the main enzyme that removes topological interlinks that persist between DNA replication products after their synthesis, leads to similar chromosome bridges. Here, we follow the catenation status of circular minichromosomes of three sizes during the S. cerevisiae cell cycle. Catenanes are produced in S-phase and, in part, they are readily resolved, aided by physical separation of sister chromatids during mitosis. Complete resolution, however, requires the condensin complex, a dependency that becomes more pronounced with increasing chromosome size. Condensin and topoisomerase II directly interact and, using purified proteins, we show that condensin stimulates DNA decatenation by topoisomerase II in vitro. Therefore, in parallel to promoting chromosome condensation, condensin facilitates topological resolution of sister chromatids to secure their successful segregation to daughter cells during cell division.

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