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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 |
Appears in Collections: | Elements Staff Publications |
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