Essential role for nuclear PTEN in maintaining chromosomal integrity

Cell. 2007 Jan 12;128(1):157-70. doi: 10.1016/j.cell.2006.11.042.


A broad spectrum of mutations in PTEN, encoding a lipid phosphatase that inactivates the P13-K/AKT pathway, is found associated with primary tumors. Some of these mutations occur outside the phosphatase domain, suggesting that additional activities of PTEN function in tumor suppression. We report a nuclear function for PTEN in controlling chromosomal integrity. Disruption of Pten leads to extensive centromere breakage and chromosomal translocations. PTEN was found localized at centromeres and physically associated with CENP-C, an integral component of the kinetochore. C-terminal PTEN mutants disrupt the association of PTEN with centromeres and cause centromeric instability. Furthermore, Pten null cells exhibit spontaneous DNA double-strand breaks (DSBs). We show that PTEN acts on chromatin and regulates expression of Rad51, which reduces the incidence of spontaneous DSBs. Our results demonstrate that PTEN plays a fundamental role in the maintenance of chromosomal stability through the physical interaction with centromeres and control of DNA repair. We propose that PTEN acts as a guardian of genome integrity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Nucleus / metabolism*
  • Centromere / metabolism
  • Chromosomal Instability*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Mammalian / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • E2F1 Transcription Factor / metabolism
  • Fibroblasts / cytology
  • Humans
  • Mice
  • Mutant Proteins / metabolism
  • PTEN Phosphohydrolase / deficiency
  • PTEN Phosphohydrolase / metabolism*
  • Protein Binding
  • Protein Transport
  • Rad51 Recombinase / metabolism


  • Chromosomal Proteins, Non-Histone
  • E2F1 Transcription Factor
  • Mutant Proteins
  • centromere protein C
  • Rad51 Recombinase
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Pten protein, mouse