Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability

Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation

Faithful segregation of chromosomes in mammalian cells requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying cyclin-dependent kinase 1 (CDK1) activation, which triggers mitotic entry, have been extensively studied, the regulatory mechanisms that couple CDK1-cyclin B activ...

Mechanisms of Chromosomal Instability

Most solid tumors are aneuploid, having a chromosome number that is not a multiple of the haploid number, and many frequently mis-segregate whole chromosomes in a phenomenon called chromosomal instability (CIN). CIN positively correlates with poor patient prognosis, indicating that reduced mitotic fidelity contributes to cancer progression by increasing genetic diversity among tumor cells. Here...

Linking stem cells to chromosomal instability.

The discovery of a stem cell population in human neoplasias has given a new impulse to the study of the origins of cancer. The tissue compartment in which transformation first occurs likely comprises stem cells, since these cells need to consolidate the short-term and long-term requisites of tissue renewal. Because of their unique role, stem cells have a combination of characteristics that make...

Mouse Models for Chromosomal Instability

Chromosomal instability and human cancer.

Genetic instability is a defining feature of human cancer. The main type of genetic instability, chromosomal instability (CIN), enhances the rate of gross chromosomal changes during cell division. CIN is brought about by mutations of CIN genes, i.e. genes that are involved in maintaining the genomic integrity of the cell. A major question in cancer genetics is whether genetic instability is a c...