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p53 responsive elements in human retrotransposons

Oncogene volume 28, pages 3857–3865 (2009)Cite this article

Abstract

Long interspersed nuclear elements-1 (L1s) are highly repetitive DNA elements that are capable of altering the human genome through retrotransposition. To protect against L1 retroposition, the cell downregulates the expression of L1 proteins by various mechanisms, including high-density cytosine methylation of L1 promoters and DICER-dependent destruction of L1 mRNAs. In this report, a large number of p53 responsive elements, or p53 DNA binding sites, were detected in L1 elements within the human genome. At least some of these p53 responsive elements are functional and can act to increase the levels of L1 mRNA expression. The p53 protein can directly bind to a short 15-nucleotide sequence within the L1 promoter. This p53 responsive element within L1 is a recent addition to evolution, appearing ∼20 million years ago. This suggests an interplay between L1 elements, which have a rich history of causing changes in the genome, and the p53 protein, the function of which is to protect against genomic changes. To understand these observations, a model is proposed in which the increased expression of L1 mRNAs by p53 actually increases, rather than decreases, the genomic stability through amplification of p53-dependent processes for genomic protection.

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Acknowledgements

This work was primarily supported by the Verto Institute, with additional support provided by NIH Grant nos K25HG00060, R01EY015771, R01MH44292 and P01CA87497.

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Authors and Affiliations

  1. Raymond and Beverly Sackler Foundation, New Brunswick, NJ, USA

    C R Harris & R Normart

  2. Cancer Institute of New Jersey and Department of Pediatrics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA

    C R Harris

  3. Department of Epidemiology and Public Health, Yale University, New Haven, CT, USA

    A DeWan & J Hoh

  4. Department of Biological Sciences, Columbia University, New York, NY, USA

    A Zupnick & C Prives

  5. Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, USA

    A Gabriel

  6. Institute for Advanced Study, School of Natural Sciences, Princeton, NJ, USA

    A J Levine

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  1. C R Harris
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  8. J Hoh
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Correspondence to A J Levine.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Harris, C., DeWan, A., Zupnick, A. et al. p53 responsive elements in human retrotransposons. Oncogene 28, 3857–3865 (2009). https://doi.org/10.1038/onc.2009.246

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