Cells deleted for Brca2 COOH terminus exhibit hypersensitivity to gamma-radiation and premature senescence.
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 gamma-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 gamma-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.
Lexicon Genetics, Inc., The Woodlands, Texas 77381, USA.
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M
Morimatsu
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G
Donoho
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P
Hasty
D000818:Animals; D024682:BRCA2 Protein; D002455:Cell Division / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D005091:Exons; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D005720:Gamma Rays; D017353:Gene Deletion; D018390:Gene Targeting; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D024682:BRCA2 Protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors