Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.celrep.2021.108892
Title: On the role of p53 in the cellular response to aneuploidy
Authors: Narkar, Akshay
Johnson, Blake A.
Bharne, Pandurang
Zhu, Jin
Padmanaban, Veena
Biswas, Debojyoti
Fraser, Andrew
Iglesias, Pablo A.
Ewald, Andrew J.
Li, Rong 
Keywords: aneuploidy
G1 arrest
mitosis
organoids
p53
Issue Date: 1-Mar-2021
Publisher: Elsevier B.V.
Citation: Narkar, Akshay, Johnson, Blake A., Bharne, Pandurang, Zhu, Jin, Padmanaban, Veena, Biswas, Debojyoti, Fraser, Andrew, Iglesias, Pablo A., Ewald, Andrew J., Li, Rong (2021-03-01). On the role of p53 in the cellular response to aneuploidy. Cell Reports 34 (12) : 108892. ScholarBank@NUS Repository. https://doi.org/10.1016/j.celrep.2021.108892
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: By investigating how various cell lines and organotypic cultures respond to the induction of aneuploidy, Narkar et al. show that p53 does not constitute a universal surveillance mechanism against aneuploidy. p53 prevents aneuploidy by limiting mitotic errors in colon organoids. © 2021 The AuthorsMost solid tumors are aneuploid, and p53 has been implicated as the guardian of the euploid genome. Previous experiments using human cell lines showed that aneuploidy induction leads to p53 accumulation and p21-mediated G1 cell cycle arrest. We find that adherent 2-dimensional (2D) cultures of human immortalized or cancer cell lines activate p53 upon aneuploidy induction, whereas suspension cultures of a human lymphoid cell line undergo a p53-independent cell cycle arrest. Surprisingly, 3D human and mouse organotypic cultures from neural, intestinal, or mammary epithelial tissues do not activate p53 or arrest in G1 following aneuploidy induction. p53-deficient colon organoids have increased aneuploidy and frequent lagging chromosomes and multipolar spindles during mitosis. These data suggest that p53 may not act as a universal surveillance factor restricting the proliferation of aneuploid cells but instead helps directly or indirectly ensure faithful chromosome transmission likely by preventing polyploidization and influencing spindle mechanics. © 2021 The Authors
Source Title: Cell Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/232818
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.108892
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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