Time-dependent gene regulation by the tumor-suppressor protein p53 conferred by DNA flexibility

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My scientific research since my PhD days involves various aspects of the sequence-dependence of the DNA double helix and its influence on binding-site recognition by regulatory transcription factors. We have shown in several systems that the structural properties of DNA binding sites play a crucial role in the recognition of DNA by transcriptions factors. This mode of recognition, termed “shape readout” allows several codes to coexist simultaneously on the DNA double helix. In this study we show that functional outcome of p53-dependent gene expression is also coded on the DNA double helix. On the one hand, this will enable us to understand more how this important protein, p53, orchestrates its myriad functional outcomes to combat cellular-stress events. On the other hand, it expands our understanding how the DNA double helix, our central information hub, encodes multiple kinds of information, from coding to genes to packaging and gene regulation, within the sequence of its bases. This discovery opens avenues for designing more effective treatments for conditions where cellular stress plays a critical role, such as in cancer. By manipulating the flexibility of p53 binding sites, we may be able to fine-tune cellular responses and potentially improve the outcomes of stress-related diseases

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