Special Seminar: The ancient & insoluble problem of mitotic chromosome formation
Attempts to understand how the DNA is packaged in mitotic chromosomes are confounded by the huge size of the DNA, the incredible chromatin density in mitotic chromosomes and the complexity of the machinery that does the DNA packaging. We study this problem by combining chemical genetics, Hi-C genomic analysis, polymer modelling and electron microscopy. In our system, the entire cell population enters mitosis with
near perfect synchrony within 2 to 3 minutes of release of a G2 phase arrest. The cells are engineered so that chromosome formation is directed by single SMC complexes: cohesin, condensin I or condensin II. Our latest models reveal that chromosomes are a disorderly helix of loops created by the SMC complexes. Condensin II drives the formation of cylindrical chromosomes, but is restrained from achieving its ideal state by residual cohesive cohesin. The speed of loop formation, in vivo is very similar to the speed of loop formation in in vitro systems but the process must be more complicated in vivo. Our electron microscopy analysis reveals that nucleosomes achieve a near millimolar level in mitotic chromosomes. In vitro, SMC motors are fast but weak, so how do they function in such a dense environment? The data from our electron microscopy and modelling are most consistent with chromosome formation involving a combination of looping by SMC complexes and chromatin
phase separation. However, the chromatin concentration in chromosomes is much higher than the concentration of nucleosomes in phase-separated droplets in vitro. Thus, despite over 140 years of study, the essential mysteries of miotic chromosome formation remain elusive.
Date: 10 June 2024, 11:00 (Monday, 8th week, Trinity 2024)
Venue: Dorothy Crowfoot Hodgkin Building, off South Parks Road OX1 3QU
Venue Details: DCHB Seminar Room 1
Speaker: William C Earnshaw (Wellcome Centre for Cell Biology)
Organising department: Department of Biochemistry
Organiser contact email address: madhusudhan.srinivasan@bioch.ox.ac.uk
Host: Madhu Srinivasan (University of Oxford)
Booking required?: Not required
Audience: Members of the University only
Editor: Pamela Mupita-Kupeta