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Publication : A role for Brca1 in chromosome end maintenance.

First Author  McPherson JP Year  2006
Journal  Hum Mol Genet Volume  15
Issue  6 Pages  831-8
PubMed ID  16446310 Mgi Jnum  J:106759
Mgi Id  MGI:3619484 Doi  10.1093/hmg/ddl002
Citation  McPherson JP, et al. (2006) A role for Brca1 in chromosome end maintenance. Hum Mol Genet 15(6):831-8
abstractText  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.
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