The role of DNA damage responses in p53 biology
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The tumour suppressor p53 is a central player in cellular DNA damage responses. P53 is upregulated and activated by genotoxic stress and induces a transcriptional programme with effectors promoting apoptosis, cell cycle arrest, senescence and DNA repair. For the best part of the last three decades, these DNA damage-related programmes triggered by p53 were unequivocally regarded as the major if not sole mechanism by which p53 exerts its tumour suppressor function. However, this interpretation has been challenged by a number of recent in vivo studies, demonstrating that mice which are defective in inducing p53-dependent apoptosis, cell cycle arrest and senescence suppress thymic lymphoma as well as wild-type p53 expressing animals. Consequently, the importance of DNA damage responses for p53-mediated tumour suppression has been questioned. In this review, I summarize current knowledge on p53-controlled DNA damage responses and argue that these activities, while their role has certainly changed, remain an important feature of p53 biology with relevance for cancer therapy and tumour suppression.
KeywordsP53 DNA damage Tumour suppression Cancer therapy Apoptosis Cell cycle arrest Senescence DNA Repair
Work on DNA damage responses in my laboratory has been supported by Grants from Cure Cancer Australia Foundation, Cancer Institute New South Wales, Anthony Rothe Memorial Trust and Tour de Cure.
Conflict of interest
The author declares that he has no conflict of interest.
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