The nucleolus stress response is coupled to an ATR-Chk1-mediated G2 arrest
Department of Biochemistry and Molecular Pharmacology; Program in Cell and Developmental Dynamics
Medical Subject Headings
Cell Nucleolus; Cell Cycle; Cell Cycle Proteins
Cell and Developmental Biology | Cellular and Molecular Physiology | Molecular Biology
We report experiments on the connection between nucleolar stress and cell cycle progression, using HeLa cells engineered with the fluorescent ubiquitinylation-based cell cycle indicator. Nucleolar stress elicited by brief exposure of cells to a low concentration of actinomycin D that selectively inhibits rRNA synthesis had no effect on traverse of G1 or S, but stalled cells in very late interphase. Additional experiments revealed that a switch occurs during a specific temporal window during nucleolar stress and that the subsequent cell cycle arrest is not triggered simply by the stress-induced decline in the synthesis of rRNA or by a ribosome starvation phenomenon.
Further experiments revealed that this nucleolus stress-induced cell cycle arrest involves the action of a G2 checkpoint mediated by the ataxia telangiectasia and Rad3-related protein (ATR)-checkpoint kinase 1 (Chk1) pathway.
Based on analysis of the cell cycle stages at which this nucleolar stress effect is put into action, to become manifest later, our results demonstrate a feedforward mechanism that leads to G2 arrest and identify ATR and Chk1 as molecular agents of the requisite checkpoint.
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Citation: Mol Biol Cell. 2013 May;24(9):1334-42. doi: 10.1091/mbc.E12-12-0881. Link to article on publisher's site
Ma, Hanhui and Pederson, Thoru, "The nucleolus stress response is coupled to an ATR-Chk1-mediated G2 arrest" (2013). University of Massachusetts Medical School Faculty Publications. 60.