Frank Uhlmann

Chromosome segregation during mitosis

All eukaryotic cells inherit their genome in the form of chromosomes during mitotic and meiotic cell divisions. We analyse the mechanisms involved in faithful chromosome inheritance mainly using budding yeast mitosis as a model.

After DNA replication during S-phase the two copies of each chromosome, the sister chromatids, stay connected with each other. This cohesion between sister chromatids is the basis for their bipolar alignment on the metaphase plate later in mitosis.

Sister chromatid cohesion is mediated by a chromosomal multi-subunit protein complex, called 'cohesin'. Cohesin forms a large proteinaceous ring that may embrace two sister chromatids. How the cohesin ring is loaded onto DNA, and how cohesin is converted into a physical link between sister chromatids as the replication fork moves along chromosomes, is still mysterious.

We also study the function of a second chromosomal protein complex, related to cohesin, named 'condensin'. The condensin complex mediates compaction of centimetre long DNA molecules into micrometre-sized eukaryotic chromosomes for successful segregation in mitosis. Little is known about how and where condensin binds to DNA, and how condensin promotes mitotic chromosome condensation.

Our approaches to understand chromosome cohesion and condensation involve biochemical reconstitution of the cohesin complex and its binding to DNA, as well as genetic and cell biological studies in life yeast.

References

Lengronne A, et al. Cohesin relocation from sites of chromosomal loading to places of convergent transcription. Nature 2004; 430: 573-578.

Lengronne A, McIntyre J, Katou Y, Kanoh Y, Hopfner K-P, Shirahige K and Uhlmann F. Establishment of sister chromatid cohesion at the S. cerevisiae replication fork. Mol Cell 2006; 23: 787-799.

McIntyre J, Muller EGD, Weitzer S, Snydsman BE, Davis TN and Uhlmann F. In vivo analysis of cohesin architecture using FRET in the budding yeast Saccharomyces cerevisiae. EMBO J 2007; 26: 3783-3793.