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On the role of p53 in the cellular response to aneuploidy.

Cell reports (2021-03-25)
Akshay Narkar, Blake A Johnson, Pandurang Bharne, Jin Zhu, Veena Padmanaban, Debojyoti Biswas, Andrew Fraser, Pablo A Iglesias, Andrew J Ewald, Rong Li
ABSTRACT

Most 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nocodazole, ≥99% (TLC), powder
Sigma-Aldrich
Collagenase from Clostridium histolyticum, suitable for release of rat epididymal adipocytes and hepatocytes (for methodology see Type II and Type IV), Type VIII, 0.5-5.0 FALGPA units/mg solid, ≥125 CDU/mg solid
Sigma-Aldrich
Nutlin-3, ≥98% (HPLC), powder