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Fred Bunz

Publications and source records attributed to Fred Bunz.

4 recordsLinked to original sources
PubMed2003

The Chk2 tumor suppressor is not required for p53 responses in human cancer cells.

Ionizing radiation damages chromosomal DNA and activates p53-dependent transcription in mammalian cells. The Chk2 protein kinase has been hypothesized to be the primary mediator of this response. We have rigorously tested this hypothesis in human cells by disrupting the CHK2 gene through homologous recombination. We found that the p53 response was unexpectedly robust in such cells. Phosphorylation of p53 at serine 20, accumulation of p53 protein, transcriptional activation of p53 target genes, and cell cycle arrest and apoptotic death phenotypes were completely intact regardless of CHK2 status. Our results indicate that Chk2 kinase is not required for p53 activation in human cells and explain why CHK2 and TP53 mutations can jointly occur in human tumors.

Checkpoint Kinase 2↗
PubMed2002

Targeted inactivation of p53 in human cells does not result in aneuploidy.

Because p53 mutation and aneuploidy usually coexist, it has been suggested that p53 inactivation leads to aneuploidy. We have rigorously tested this hypothesis in diploid human cell lines in which p53 was experimentally inactivated by targeted homologous recombination. Cells completely deficient in p53 did not become aneuploid, although a slight tendency toward tetraploidization was observed. No increased rates of numerical or structural chromosomal instabilities were observed in the p53-deficient cells. Rates of sister chromatid exchange and homologous recombination were also unaffected by p53 status. These results show that inactivation of p53 does not, in and of itself, lead to the development of aneuploidy.

Alleles↗
PubMed2002

Human cell knockouts.

One of the most productive areas of biologic research has been the utilization of model organisms for the systematic study of gene function. Although the experimental manipulation of these model genetic systems has provided important insights into the function of homologous genes in humans, such studies are necessarily limited by the need to extrapolate among divergent species and cell types. Researchers have now begun to apply the technology of gene targeting to human cell lines. Recently, studies of human cell knockouts have yielded important new information about how the cell cycle is regulated and how this regulation can go awry in cancer cells. The targeting of human genes promises to be a powerful tool in the characterization of the molecular pathways relevant to cancer.

Animals↗