Human Molecular Genetics Advance Access published online on January 30, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl002
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1 Advanced Medical Discovery Institute, University of Toronto, Toronto, Ontario, Canada M5G 2C1; Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1
* To whom correspondence should be addressed. 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.
Received December 7, 2005
Revised January 21, 2006
Accepted January 21, 2006
Article
A role for Brca1 in chromosome end maintenance
J. Peter McPherson 1,
M. Prakash Hande 2 *,
Anuradha Poonepalli 3,
Benedicte Lemmers 1,
Elzbieta Zablocki 1,
Eva Migon 1,
Amro Shehabeldin 1,
Annaliza Porras 1,
Jana Karaskova 4,
Bisera Vukovic 4,
Jeremy Squire 4,
and
Razqallah Hakem 1 *
2 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Singapore; Oncology Research Institute, National University Medical Institutes, Singapore 117597
3 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597
4 Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1
M. Prakash Hande, E-mail: phsmph{at}nus.edu.sg
Razqallah Hakem, E-mail: rhakem{at}uhnres.utoronto.ca
Abstract 
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