The ATM-p53 pathway suppresses aneuploidy-induced tumorigenesis

Min Li, Xiao Fang, Darren J Baker, Linjie Guo, Xue Gao, Zhubo Wei, Shuhua Han, Jan Van Deursen, Pumin Zhang

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The spindle assembly checkpoint (SAC) is essential for proper sister chromatid segregation. Defects in this checkpoint can lead to chromosome missegregation and aneuploidy. An increasing body of evidence suggests that aneuploidy can play a causal role in tumorigenesis. However, mutant mice that are prone to aneuploidy have only mild tumor phenotypes, suggesting that there are limiting factors in the aneuploidy-induced tumorigenesis. Here we provide evidence that p53 is such a limiting factor.Weshow that aneuploidy activates p53 and that loss of p53 drastically accelerates tumor development in two independent aneuploidy models. The p53 activation depends on the ataxia-telangiectasia mutated (ATM) gene product and increased levels of reactive oxygen species. Thus, the ATM-p53 pathway safeguards not only DNA damage but also aneuploidy.

Original languageEnglish (US)
Pages (from-to)14188-14193
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number32
DOIs
StatePublished - Aug 10 2010

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Ataxia Telangiectasia
Aneuploidy
Carcinogenesis
M Phase Cell Cycle Checkpoints
Chromatids
DNA Damage
Reactive Oxygen Species
Neoplasms
Chromosomes
Phenotype
Genes

ASJC Scopus subject areas

  • General

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The ATM-p53 pathway suppresses aneuploidy-induced tumorigenesis. / Li, Min; Fang, Xiao; Baker, Darren J; Guo, Linjie; Gao, Xue; Wei, Zhubo; Han, Shuhua; Van Deursen, Jan; Zhang, Pumin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 32, 10.08.2010, p. 14188-14193.

Research output: Contribution to journalArticle

Li, Min ; Fang, Xiao ; Baker, Darren J ; Guo, Linjie ; Gao, Xue ; Wei, Zhubo ; Han, Shuhua ; Van Deursen, Jan ; Zhang, Pumin. / The ATM-p53 pathway suppresses aneuploidy-induced tumorigenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 32. pp. 14188-14193.
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