Principles of genome organization underlying chromosome segregation during mitosis and meiosis

Abstract

Faithful chromosome segregation is fundamental to maintaining genome stability. Errors in this process lead to aneuploidy, an abnormal number of chromosomes, that is associated with many cancers and causes birth defects, miscarriages, and infertility. During mitosis, sister chromatids are evenly segregated to produce genetically identical daughter cells, whereas meiosis partitions the genome through two consecutive divisions that generate haploid gametes. However, meiosis is particularly error-prone, with aneuploidy affecting roughly 1% of human sperm and up to 30% of oocytes.

Our research seeks to uncover the molecular mechanisms that ensure accurate chromosome segregation in both mitosis and meiosis. We combine the genetic and experimental tractability of yeast with complementary studies in frog, mouse, bovine and human oocytes. Guided by specific mechanistic questions, we employ diverse cell biological, genomic, proteomic, and biochemical approaches. Our work has revealed unexpected roles for pericentromeres—chromosomal domains flanking centromeres—and distinct kinetochore functions that orient chromosomes and safeguard segregation fidelity.

In this seminar, I will present our recent findings on chromosome organisation and its importance for accurate segregation, highlighting conserved principles that ensure faithful genome inheritance across species.