Chromosome Research

, 15:1001

Tpp1/Acd maintains genomic stability through a complex role in telomere protection

Authors

  • Tobias Else
    • Department of Internal Medicine, Division of Endocrinology and MetabolismThe University of Michigan
  • Brian K. Theisen
    • Department of PathologyUniversity of Michigan Medical School
  • Yipin Wu
    • Department of PathologyUniversity of Michigan Medical School
  • Janna E. Hutz
    • Department of Pediatrics, Division of GeneticsThe University of Michigan
  • Catherine E. Keegan
    • Department of Pediatrics, Division of GeneticsThe University of Michigan
  • Gary D. Hammer
    • Department of Internal Medicine, Division of Endocrinology and MetabolismThe University of Michigan
    • Department of Molecular and Integrative PhysiologyThe University of Michigan
    • Department of PathologyUniversity of Michigan Medical School
Article

DOI: 10.1007/s10577-007-1175-5

Cite this article as:
Else, T., Theisen, B.K., Wu, Y. et al. Chromosome Res (2007) 15: 1001. doi:10.1007/s10577-007-1175-5

Abstract

Telomeres serve to protect the ends of chromosomes, and failure to maintain telomeres can lead to dramatic genomic instability. Human TPP1 was identified as a protein which interacts with components of a telomere cap complex, but does not directly bind to telomeric DNA. While biochemical interactions indicate a function in telomere biology, much remains to be learned regarding the roles of TPP1 in vivo. We previously reported the positional cloning of the gene responsible for the adrenocortical dysplasia (acd) mouse phenotype, which revealed a mutation in the mouse homologue encoding TPP1. We find that cells from homozygous acd mice harbor chromosomes fused at telomere sequences, demonstrating a role in telomere protection in vivo. Surprisingly, our studies also reveal fusions and radial structures lacking internal telomere sequences, which are not anticipated from a simple deficiency in telomere protection. Employing spectral karyotyping and telomere FISH in a combined approach, we have uncovered a striking pattern; fusions with telomeric sequences involve nonhomologous chromosomes while those lacking telomeric sequences involve homologues. Together, these studies show that Tpp1/Acd plays a vital role in telomere protection, but likely has additional functions yet to be defined.

Key words

chromosome fusionfluorescence in-situ hybridizationgenome instabilityspectral karyotypingtelomere

Copyright information

© Springer 2007