Implications of aneuploidy for stem cell biology and brain Biology Diagrams Aneuploidy often confers a proliferative disadvantage with a delay in the G1 and S phases of the cell cycle, probably due to delayed accumulation of cyclins 63,68,70,73,74,75. The proliferation
A key to understanding how aneuploidy affects cell behavior is the concept of gene dosage (including those harboring DNA damage) are also subject to several other fates, such as cell-cycle delays, DNA condensation defects, inappropriate mitotic entry, senescence, and even immunological recognition and destruction (Andriani et al Aneuploidy, an aberrant number of chromosomes, has been recognized as a feature of human malignancies for over a century, but compelling evidence for causality was largely lacking until mouse models for chromosome number instability were used. Aneuploidy in health, disease, and aging J Cell Biol. 2013 Apr 1;201(1) Cell Cycle Proteins However, weakening SAC function allows for premature cell-cycle progression to anaphase and dramatically increases the probability of whole chromosome mis-segregation leading to aneuploidy. Cancer is the most common human disease characterized by somatic aneuploidy (both whole and structural) with over 90% of solid tumors estimated to be
Effects of aneuploidy on cell behaviour and function Biology Diagrams
Cell cycle checkpoints delay chromosome segregation until DNA replication has been completed and sister chromatids are properly aligned at the metaphase plate. aneuploidy is a hallmark of cancer, a disease of increased cell proliferation . Greater than 90% of solid tumors and 75% of hematopoietic cancers have gained or lost entire In mouse and induced pluripotent stem cell Down syndrome models, an extra copy of this gene could recapitulate a number of Down syndrome-associated defects, whereas its inhibition rescued the Here, p53-dependent cell cycle arrest would be induced after structural, rather than numerical, aneuploidy and only once a critical threshold of DNA damage is reached.
Cell division errors that result in aneuploidy. Mitotic cells mis-segregate one or multiple chromosomes by (a) mutations to the spindle assembly checkpoint pathway, where aberrantly attached chromosomes do not trigger a cell cycle arrest, (b) premature loss of chromatid cohesion, where single chromatids attach to microtubules and are randomly segregated, (c) merotelic attachment, where
