A role for Brca1 in chromosome end maintenance

Hum Mol Genet. 2006 Mar 15;15(6):831-8. doi: 10.1093/hmg/ddl002. Epub 2006 Jan 30.

Abstract

The role of BRCA1 in breast and ovarian tumor suppression has been primarily ascribed to the maintenance of genome integrity. BRCA1 interacts with components of the non-homologous end-joining pathway previously shown to play a role in telomere maintenance in yeast. Here, we provide evidence that links Brca1 with telomere integrity. Brca1(-/-) T-cells display telomere dysfunction in both loss of telomere repeats as well as defective telomere capping. Loss of Brca1 synergizes with p53 deficiency in the onset and frequency of tumorigenesis. Karyotyping of tBrca1(-/-)p53(-/-) thymic lymphomas revealed the presence of telomere dysfunction accompanied by clonal chromosomal translocations. The telomere dysfunction phenotype in Brca1-deficient cells suggests that loss of telomere integrity might contribute to chromosome end dysfunction and permit the formation of potentially oncogenic translocations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA1 Protein / deficiency
  • BRCA1 Protein / genetics
  • BRCA1 Protein / physiology*
  • In Situ Hybridization, Fluorescence
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Phenotype
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere / pathology
  • Thymoma / genetics
  • Thymoma / pathology
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics

Substances

  • BRCA1 Protein
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Bcl2 protein, mouse