The nucleolus stress response is coupled to an ATR-Chk1-mediated G2 arrest
UMass Chan Affiliations
Program in Cell and Developmental DynamicsDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2013-05-01Keywords
Cell NucleolusCell Cycle
Cell Cycle Proteins
Cell and Developmental Biology
Cellular and Molecular Physiology
Molecular Biology
Metadata
Show full item recordAbstract
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.Source
Mol Biol Cell. 2013 May;24(9):1334-42. doi: 10.1091/mbc.E12-12-0881. Link to article on publisher's siteDOI
10.1091/mbc.E12-12-0881Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30330PubMed ID
23447702Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1091/mbc.E12-12-0881