A role for Brca1 in chromosome end maintenance | Zendy

J. Peter McPherson | Zendy; M. Prakash Hande | Zendy; Anuradha Poonepalli | Zendy; Bénédicte Lemmers | Zendy; Elzbieta Zablocki | Zendy; Eva Migon | Zendy; Amro Shehabeldin | Zendy; Annaliza Porras | Zendy; Jana Karásková | Zendy; Bisera Vukovic | Zendy; Jeremy A. Squire | Zendy; Razqallah Hakem | Zendy

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A role for Brca1 in chromosome end maintenance

Author(s) -

J. Peter McPherson,

M. Prakash Hande,

Anuradha Poonepalli,

Bénédicte Lemmers,

Elzbieta Zablocki,

Eva Migon,

Amro Shehabeldin,

Annaliza Porras,

Jana Karásková,

Bisera Vukovic,

Jeremy A. Squire,

Razqallah Hakem

Publication year - 2006

Publication title -

human molecular genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.811

H-Index - 276

eISSN - 1460-2083

pISSN - 0964-6906

DOI - 10.1093/hmg/ddl002

Subject(s) - telomere , biology , chromosomal translocation , carcinogenesis , phenotype , genetics , cancer research , dna damage , dna repair , genome instability , chromosome , microbiology and biotechnology , dna , cancer , gene

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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