Single-cell live microscopy studies uncover the harmful impact of human genomic variations in a kinetochore protein, Astrin.

Session

Stream 5: Imaging in Development and Disease

Authors

Dr Asifa Islam (1), Prof Viji Draviam (1)

Affiliations

1. Queen Mary University of London

Keywords

Live-cell microscopy

Mitosis

Kinetochore

Genomic variation

Abstract text

During cell division, chromosomes are captured by microtubules via a multiprotein complex called the kinetochore. Taking advantage of single-cell live microscopy methods, we investigate the impact of human genomic variations in kinetochore proteins that can cause pregnancy loss and developmental defects such as primary microcephaly (MCPH) and cancer-susceptible disorder mosaic variegated aneuploidy (MVA). The kinetochore protein Astrin is specifically recruited to kinetochores following their attachment to microtubule-ends, and its arrival stabilizes chromosome-microtubule attachments.  Human genomic variations in Astrin are known, but their impact on chromosome segregation has not been studied. We have used a combination of cell biology techniques to study the subcellular localization and cell cycle impact of Astrin variants- p.Q1012* and p.L7Qfs*21 - identified in a screen of healthy individuals and Astrin p.E755K found in cancer cells. We will present our quantitative cell biology findings that explain the occurrence of Astrin p.L7Qfs*21, but not p.Q1012, homozygotes within a healthy general population.