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PLoS Genet. 2009 Oct;5(10):e1000680. doi: 10.1371/journal.pgen.1000680. Epub 2009 Oct 9.

p63 and p73 transcriptionally regulate genes involved in DNA repair.

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Department of Molecular and Cellular Oncology, Graduate School of Biomedical Sciences, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.


The p53 family activates many of the same genes in response to DNA damage. Because p63 and p73 have structural differences from p53 and play distinct biological functions in development and metastasis, it is likely that they activate a unique transcriptional network. Therefore, we performed a genome-wide analysis using cells lacking the p53 family members after treatment with DNA damage. We identified over 100 genes involved in multiple pathways that were uniquely regulated by p63 or p73, and not p53. Further validation indicated that BRCA2, Rad51, and mre11 are direct transcriptional targets of p63 and p73. Additionally, cells deficient for p63 and p73 are impaired in DNA repair and p63+/-;p73+/- mice develop mammary tumors suggesting a novel mechanism whereby p63 and p73 suppress tumorigenesis.

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Conflict of interest statement

The authors have declared that no competing interests exist.

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