Here, using a tunable system of chromosome mis-segregation, we show that mitotic errors trigger nuclear deformation, nuclear softening, and lamin and heterochromatin alterations, leading to rapid p53/p21 activation upon mitotic exit in response to changes in nuclear mechanics. We identify mTORC2 and...
for BRCA1- and BRCA2-deficient cells. Unlike PARP inhibition that increases replication-induced DNA double-strand breaks and radial chromosomes, depleting CIP2A or disrupting its interaction with TOPBP1 increases micronuclei and chromosomal missegregation, revealing a mitotic target for BRCA-mutated ...
2010. Chromosome missegregation causes colon cancer by APC loss of heterozygosity. Cell Cycle. 9:1711-1716. doi:10.4161/cc.9.9.11314Baker DJ,van Deursen JM.Chromosome missegregation causes colon cancer by APC loss of heterozygosity. Cell Cycle . 2010...
36,37but can differ between chromosomes of near-identical size. In support of this, four out of five acrocentric chromosomes (14, 15, 21 and 22), which reside near the centrally located nucleoli, had low mis-segregation frequencies (Fig.1c). ...
(unlike other types of mis-attachments); (iii) it can lead to chromosome mis-segregation, and, hence,aneuploidy. A number of studies have recently started to unveil the cellular and molecular mechanisms involved in merotelic kinetochore formation and correction. Here, I review these studies and ...
Chromosome missegregation and DNA damage in aneuploid cells also produce pro-inflammatory signals and activate class I interferon response [10••,13,15,16]. Accumulation of cytosolic DNA activates cGAS/STING pathway and interferon production, in line with a recent evidence that inflammatory respons...
However, numerous cellular and/or genetic defects are known to impair the fidelity of mitosis and promote chromosome segregation errors and aneuploidy. Missegregation of even a single chromosome leads to the deregulated expression of hundreds to thousands of genes, including many that are involved in...
GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 ...
2020). Interestingly, it has been found that tissue architecture can impact chromosome segregation fidelity (Knouse et al. 2018). In particular, when mouse epithelial cells were cultured as 3D spheroids the rates of chromosome mis-segregation were very low, but this rate increased to ~7% in 2D...
Bottom: Correlation between RPTEC screen gain selection frequency (average of two screens) and RPTEC chromosome mis-segregation frequency with reversine treatment at 48 h. Pearson’s correlation coefficient squared (top: r2 = 0.005, bottom: r2 = 0.002) and associated P value (top: P...