The role of the endomembrane dynamics in preserving genetic stability
Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC)
Most solid tumours are aneuploid, with higher rates of CIN, so understanding the mechanisms of chromosome missegregation is an important goal of cancer cell biology. Furthermore, mitotic errors can also lead to micronuclei (MN) formation, which is susceptible to nuclear envelope rupture and can result in extensive genomic rearrangements, such as those commonly observed in chromothripsis. While the spindle mechanics that ensure proper genome segregation during cell division have been extensively studied, less attention has been given to other structures within mitotic cells, such as intracellular membranes and organelles, collectively known as endomembranes, including the nuclear envelope and Golgi remnants, endoplasmic reticulum (ER), and vesicles. Recent studies from our lab and others have shown that endomembranes, particularly the ER, can impair chromosome dynamics and promote aneuploidy and MN formation. Therefore, our work is at the forefront of an exciting new area of cell biology, and the emerging understanding is that endomembranes are not passive actors in mitosis but rather that their organisation is regulated to maintain the genome integrity of every metazoan cell division.