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Nucleic Acids Research Advance Access originally published online on March 9, 2009
Nucleic Acids Research 2009 37(8):2688-2698; doi:10.1093/nar/gkp110
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Nucleic Acids Research, 2009, Vol. 37, No. 8 2688-2698
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gene Regulation, Chromatin and Epigenetics

DNA damage induced p53 downregulates Cdc20 by direct binding to its promoter causing chromatin remodeling

Taraswi Banerjee, Somsubhra Nath and Susanta Roychoudhury*

Molecular and Human Genetics Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata 700032, India

*To whom correspondence should be addressed. Tel: +91 33 2499 5823/5000; Fax: +91 33 2473 3967/5197; Email: susanta{at}iicb.res.in or susantarc{at}gmail.com

Received July 31, 2008. Accepted February 9, 2009.

CDC20 is a critical molecule in the Spindle Assembly Checkpoint (SAC). It activates the Anaphase promoting complex and helps a dividing cell to proceed towards Anaphase. CDC20 is overexpressed in many tumor cells which cause chromosomal instability. There have been limited reports on the mechanism of SAC's response to genotoxic stress. We show that ectopically expressed p53 or DNA damage induced endogenous p53 can downregulate Cdc20 transcriptionally. We have identified a consensus p53-binding site on the Cdc20 promoter and have shown that it is being used by p53 to bind the promoter and bring about chromatin remodeling thereby repressing Cdc20. Additionally, p53 also downregulates Cdc20 promoter through CDE/CHR element, but in a p21 independent manner. This CDE/CHR element-mediated downregulation occurs only under p53 overexpressed condition but not in the context of DNA damage. The present results suggest that the two CCAAT elements in the Cdc20 promoter are not used by p53 to downregulate its activity, as reported earlier.


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