Chinese hamster cell mutant, V-C8, a model for analysis of Brca2 function

Mutat Res. 2006 Aug 30;600(1-2):79-88. doi: 10.1016/j.mrfmmm.2006.03.001. Epub 2006 Apr 27.


The previously described Chinese hamster cell mutant V-C8 that is defective in Brca2 shows a very complex phenotype, including increased sensitivity towards a wide variety of DNA damaging agents, chromosomal instability, abnormal centrosomes and impaired formation of Rad51 foci in response to DNA damage. Here, we demonstrate that V-C8 cells display biallelic nonsense mutations in Brca2, one in exon 15 and the other in exon 16, both resulting in truncated Brca2 proteins. We generated several independent mitomycin C (MMC)-resistant clones from V-C8 cells that had acquired an additional mutation leading to the restoration of the open reading frame of one of the Brca2 alleles. In two of these revertants, V-C8-Rev 1 and V-C8-Rev 6, the reversions lead to the wild-type Brca2 sequence. The V-C8 revertants did not gain the entire wild-type phenotype and still show a 2.5-fold increased sensitivity to mitomycin C (MMC), higher levels of spontaneous and MMC-induced chromosomal aberrations, as well as abnormal centrosomes when compared to wild-type cells. Our results suggest that Brca2 heterozygosity in hamster cells primarily gives rise to sensitivity to DNA cross-linking agents, especially chromosomal instability, a feature that might also be displayed in BRCA2 heterozygous mutation carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism
  • Cell Line*
  • Centrosome / metabolism
  • Chromosomal Instability*
  • Chromosome Aberrations / drug effects
  • Codon, Nonsense*
  • Codon, Terminator
  • Cricetinae
  • Cricetulus / genetics*
  • Cross-Linking Reagents / pharmacology
  • Female
  • Genes, BRCA2*
  • Heterozygote
  • Models, Genetic
  • Molecular Sequence Data
  • Phenotype
  • Rad51 Recombinase / metabolism
  • Sister Chromatid Exchange


  • BRCA2 Protein
  • Codon, Nonsense
  • Codon, Terminator
  • Cross-Linking Reagents
  • Rad51 Recombinase