Molecular mechanisms that cause aneuploidy Event

Abstract: Chromosomal instability (CIN) is a hallmark of aggressive cancers and acute drug resistance. CIN can arise from errors in the process of segregating DNA during cell division. To ensure the accurate segregation of DNA, it is essential that chromosomes are properly attached to microtubules. My research team explores a) how cells ensure proper chromosome-microtubule attachment and b) what are the oncogenic consequences of defective attachments. By developing high-resolution microscopy tools to visualize how microtubules capture chromosomes, we showed that a multi-step ‘end-on conversion’ process governs the plane of chromosome-microtubule attachment in human cells; chromosomes first attach to 'microtubule-walls' and then convert this attachment to 'microtubule-ends'. We find that a failure in end-on conversion can lead to chromosome mis-segregation. Importantly, three of the eight end-on conversion regulators we identified are already implicated in CIN found in cancers, highlighting the oncological significance of the process.