The putative Brca2-MmRad51 interaction is analyzed in mouse cells deleted for the COOH terminus of Brca2 (amino acids 3140–3328), which contains a region that associates with MmRad51 by yeast two-hybrid. These cells are hypersensitive to γ-radiation (suggesting defective recombinational repair) but not UV light (suggesting intact nucleotide excision repair) and maintain the G1-S and G2-M checkpoints after exposure to γ-irradiation. Cells deleted for the COOH terminus of Brca2 progress through the cell cycle at a similar rate as wild-type cells but undergo senescence more rapidly. These data support the hypothesis that deletion of Brca2 stimulates cancer by defective MmRad51-mediated DNA repair and not by defective cell cycle regulation.

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