The control of chromosome structure by cohesin/condensin complexes

03-DYNA-F-29: The control of chromosome structure by cohesin/condensin complexes

Abstract:

Chromosome segregation depends not only on forces provided by microtubules but also on the intricate control of chromosome morphology. Interphase chromosomes occupy defined spaces within the nucleus, sister chromatids are connected to each other during their synthesis (cohesion), and sister DNA sequences are packed into juxtaposed cyclindrical volumes (condensation) prior to their alignment on mitotic spindles. Both cohesion and condensation depend on multi-subunit complexes, cohesin and condensin respectively, which contain rod-shaped Smc proteins that form V-shaped hetero-dimers with ABC-like ATPases at the end of each arm. Smc proteins are more ancient than nucleosomes because they also control the morphology and partitioning of bacterial nucleoids. The recent finding that cohesin’s kleisin subunit connects the ATPase “heads” of Smc heterodimers suggests that cohesin might operate by trapping double helices inside a huge proteinaceous ring. We propose to investigate the molecular properties of Smc/kleisin devices and their effects on chromosome morphology. The latter will require novel light and electron microsopic techniques to probe chromosome structure. We aim to address whether all Smc/kleisin devices operate using the same fundamental principle, what this principle is, how different devices lead to different aspects of chromosome morphology, and how their activities are regulated during the cell cycle.

Project Leader:

Dr. Jan-Michael Peters
Research Institute of Molecular Pathology (IMP)
1030 Wien Austria
Phone:+43 1 797 30 882
Fax:+43 1 798 7153

Principal Investigators:

Terence David Allen, Paterson Institute for Cancer Research, Manchester, UK

Roland Eils, German Cancer Research Centre, Heidelberg, DE

Jan Ellenberg, EMBL, Heidelberg, DE

Jan Löwe, Medical Research Council, Cambridge, UK

Kim Nasmyth, University of Vienna, AT