The ATM–p53 pathway suppresses aneuploidy-induced tumorigenesis

• DOI: 10.1073/pnas.1005960107
• Publication Date: 2010-07-28T01:52:08Z
• Authors: Min Li; Xiao Fang; Darren J. Baker; Linjie Guo; Xue Gao; Zhubo Wei; Shuhua Han; Jan M. van Deursen; Pumin Zhang
• Keywords: Chromosome instability; Spindle checkpoint

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