Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb 26;44(4):420-431.
doi: 10.1016/j.devcel.2018.02.002.

Cellular Stress Associated with Aneuploidy

Affiliations
Review

Cellular Stress Associated with Aneuploidy

Jin Zhu et al. Dev Cell. .

Abstract

Aneuploidy, chromosome stoichiometry that deviates from exact multiples of the haploid compliment of an organism, exists in eukaryotic microbes, several normal human tissues, and the majority of solid tumors. Here, we review the current understanding about the cellular stress states that may result from aneuploidy. The topics of aneuploidy-induced proteotoxic, metabolic, replication, and mitotic stress are assessed in the context of the gene dosage imbalance observed in aneuploid cells. We also highlight emerging findings related to the downstream effects of aneuploidy-induced cellular stress on the immune surveillance against aneuploid cells.

Keywords: aneuploidy; metabolic stress; mitotic stress; proteotoxic stress; replication stress.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Effects of aneuploidy on the transcriptome and proteome due to the alteration of gene dosage. Changes to relative chromosome dosage (A) in aneuploidy (shown here as a euploid cell becoming trisomic for the blue chromosome) results in scaled changes to the RNA (B) and protein (C) expression level of genes carried on the aneuploid chromosome as is the case for direct effects of aneuploidy (D). However, indirect effects or trans-activating effects (E) of aneuploidy can alter the expression of genes on other chromosomes by increasing transcription factor levels to promote expression or by having an epigenetic effect such as de-silencing genes. Globular circles denote gene products that scale accordingly with chromosome number.
Figure 2.
Figure 2.
The major categories of aneuploidy-associated stresses discussed in this review. As shown by the black arrows pointing to the four stresses. Aneuploidy leads to mitotic stress such as lagging chromosomes, replication stress via stalled and delayed replication fork progression, metabolic stress usually related to increased ROS levels in the mitochondria, and proteotoxic stress that overwhelms the proteasome. In addition to aneuploidy causing stress, some of the stresses can further perpetuate aneuploidization through causing different stress and increasing CIN (black arrows pointing between stressed and back toward aneuploidization). For example, aneuploid cells may produce more ROS that can damage DNA leading to replication stress and mitotic error.

References

    1. Aivazidis S, Coughlan CM, Rauniyar AK, Jiang H, Liggett LA, Maclean KN, and Roede JR (2017). The burden of trisomy 21 disrupts the proteostasis network in Down syndrome. PloS one 12, e0176307. - PMC - PubMed
    1. Alver RC, Chadha GS, and Blow JJ (2014). The contribution of dormant origins to genome stability: from cell biology to human genetics. DNA repair 19, 182–189. - PMC - PubMed
    1. Anders KR, Kudrna JR, Keller KE, Kinghorn B, Miller EM, Pauw D, Peck AT, Shellooe CE, and Strong IJT (2009). A strategy for constructing aneuploid yeast strains by transient nondisjunction of a target chromosome. BMC Genetics 10, 36–36. - PMC - PubMed
    1. Andriani GA, Almeida VP, Faggioli F, Mauro M, Tsai WL, Santambrogio L, Maslov A, Gadina M, Campisi J, Vijg J, et al. (2016). Whole Chromosome Instability induces senescence and promotes SASP. Scientific reports 6, 35218. - PMC - PubMed
    1. Apel K, and Hirt H (2004). Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annual review of plant biology 55, 373–399. - PubMed

Publication types

LinkOut - more resources