Journal Article

A role for <i>Brca1</i> in chromosome end maintenance

J. Peter McPherson, M. Prakash Hande, Anuradha Poonepalli, Benedicte Lemmers, Elzbieta Zablocki, Eva Migon, Amro Shehabeldin, Annaliza Porras, Jana Karaskova, Bisera Vukovic, Jeremy Squire and Razqallah Hakem

in Human Molecular Genetics

Volume 15, issue 6, pages 831-838
Published in print March 2006 | ISSN: 0964-6906
Published online January 2006 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddl002
A role for Brca1 in chromosome end maintenance

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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.

Journal Article.  5567 words.  Illustrated.

Subjects: Genetics and Genomics

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