PMID: 11606409Oct 19, 2001Paper

Neither p21WAF1 nor 14-3-3sigma prevents G2 progression to mitotic catastrophe in human colon carcinoma cells after DNA damage, but p21WAF1 induces stable G1 arrest in resulting tetraploid cells

Cancer Research
P R AndreassenR L Margolis

Abstract

p21WAF1 and 14-3-3sigma, which are both transcriptional products of p53, have been reported to play a role in the G2 DNA damage checkpoint in mammalian cells. Human colon carcinoma cells, isogenic except for the presence or absence of either p21WAF1 or 14-3-3sigma (T. A. Chan et al., Genes Dev., 14: 1584-1588, 2000), are useful models for analysis of the role of these proteins in checkpoint control. Here, we have examined mitotic behavior within a single cell cycle after DNA damage in these cell lines. Our results show that p21WAF1, but not 14-3-3sigma, imposes a significant G2 delay after DNA damage. After G2 delay, we found that all isogenic cells, including those competent for both p21WAF1 and 14-3-3sigma, adapt to the DNA damage checkpoint and progress into mitosis, where they undergo incomplete chromosome segregation and reenter G1 with a tetraploid DNA content. Strikingly, our results show that p21WAF1, but not 14-3-3sigma, activates a checkpoint in response to DNA damage that prevents continued cycling of the tetraploid cells that result from a mitotic catastrophe characterized by failure to complete cell division. These results demonstrate that a tetraploid DNA content is not a reliable criterion to establish that arres...Continue Reading

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