Chromosome organization by SMC complexes
Human chromosomes are centimetres in length, but are organized
such that they fit into a cell of micrometre-scale dimensions.
Within this confined setting, chromosomes allow for tightly
controlled cellular processes such as mitosis and transcription.
These processes are to an important degree made possible by two
conserved protein complexes known as cohesin and condensin. Both
cohesin and condensin are so-called SMC complexes that by
entrapping DNA inside their ring-shaped lumens can structure
Cohesin and condensin each in its own way ensures the fidelity
of chromosome segregation. Cohesin holds together the sisters
chromatids of each chromosome and resists the pulling forces of
microtubules until all kinetochores are attached by the spindle
apparatus. Then the abrupt cleavage of cohesin rings triggers the
synchronous segregation of sister chromatids to the opposite poles
of the cell. Condensin in turn is important for chromosome
condensation. This process is required to ensure that chromosomes
are shortened enough to allow the splitting in half of the cell
during cytokinesis without DNA getting caught in the middle.
Cohesin also plays a major role in the 3D organization of
interphase chromosomes. By looping together CTCF sites along
chromosomes, cohesin has a fundamental role in transcriptional
Research in our lab centres on the mode of action of cohesin and
condensin. How do these complexes entrap and release DNA? How does
cohesin know which DNAs to hold together to confer sister chromatid
cohesion? How does condensin drive mitotic chromosome condensation?
And how does cohesin contribute to the formation of the often
megabase-sized loops that shape interphase chromosomes? These are
the kind of questions that keep us awake at night and drive our
research. We are addressing such questions using a combination of
genetics, biochemistry and imaging, using both budding yeast and