Molecular mechanisms of centromere inheritance and kinetochore function

The integrity of life relies on the ability of cells to faithfully pass on their genetic information in the form of chromosomes to daughter cells when they divide. Aberrant chromosome distribution leads to daughter cells with an abnormal chromosomal number, a state called aneuploidy. Aneuploidy is often implicated in cancer and causes infertility, miscarriages and birth defects such as Down's syndrome. The key protein machinery that facilitates chromosome distribution to daughter cells is called the kinetochore, which is assembled on a specialised chromosomal site called the centromere. Kinetochores physically attach chromosomes to filamentous structures called microtubules to achieve chromosome separation. A large number of different proteins regulate these biological processes.

We aim to understand how protein machineries establish and maintain centromere marks on chromosomes and how kinetochores assembled on them help in distributing chromosomes equally and identically to daughter cells. We will do this by determining and analysing structures of centromere-associated molecular machines as they interact with their binding-partners.

Understanding the mechanisms that ensure accurate chromosome separation is crucial in fighting several important disorders.