Essential role for nuclear PTEN in maintaining chromosomal integrity. Academic Article uri icon

Overview

abstract

  • 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 date

  • January 12, 2007

Research

keywords

  • Cell Nucleus
  • Chromosomal Instability
  • Chromosomes, Mammalian
  • PTEN Phosphohydrolase

Identity

Scopus Document Identifier

  • 33845999615

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2006.11.042

PubMed ID

  • 17218262

Additional Document Info

volume

  • 128

issue

  • 1