Chromosomes (pink) in the fission yeast S. pombe, one of the model organisms used in our research.

Introduction

Centimetre-long DNA molecules are compacted into micrometre-sized chromosomes for their faithful inheritance during cell divisions. The condensin complex is a major structural component of mitotic chromosomes that plays a crucial role in chromosome condensation.

In addition to its hallmark role in chromosome condensation, condensin is also required for chromosome resolution. Cells lacking condensin display anaphase chromosome bridges that are a potent cause for cell division failures. Our studies aim to shed insight into the molecular mechanisms of how condensin secures successful chromosome segregation.

We have analysed the intra-chromosomal DNA interaction landscape and how the condensin complex impacts on it. High throughput chromosome conformation capture analysis (Hi-C) is a method that maps all pairwise DNA interactions within and between chromosomes. The Hi-C difference maps shown in Figure 1a reveal increased intra-chromosomal interactions as cells enter mitosis. This increase is brought about almost entirely by the action of the condensin complex. While condensin sets up new interactions within a particular size range, 90 - 900 kb in fission yeast (Figure 1b), shorter range and longer range interactions are both suppressed.

Chromosome interaction changes during mitotic chromosome condensation

Figure 1: Chromosome interaction changes during mitotic chromosome condensation, mediated by the condensin complex. a) Hi-C difference maps, highlighting those interactions that are generated in mitosis (red). Their formation depends on condensin, as they are not observed in cells depleted for the fission yeast condensin subunit Cut14 (cut14SO). b) Interaction frequencies as a function of chromosomal distance. 1 increased, condensin-dependent, interactions in a 90 - 900 kb band; 2 decreased megabase scale interactions, probably a consequence of stiff chromosome arm formation; 3 decreased local interactions, a previously unexpected consequence of chromosome condensation.

Our research explores how the condensin complex, a member of the Structural Maintenance of Chromosomes (SMC) ATPase family, establishes interactions between more than one DNA. How does condensin select its targets at the correct interaction distance? How do condensin-mediated intra-chromosomal interactions turn DNA into a chromosome?