p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair

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...

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Autores principales: Lin, Yu-Li, Sengupta, Shomit, Gurdziel, Katherine, Bell, George W., Jacks, Tyler, Flores, Elsa R.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752189/
https://www.ncbi.nlm.nih.gov/pubmed/19816568
http://dx.doi.org/10.1371/journal.pgen.1000680
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author Lin, Yu-Li
Sengupta, Shomit
Gurdziel, Katherine
Bell, George W.
Jacks, Tyler
Flores, Elsa R.
author_facet Lin, Yu-Li
Sengupta, Shomit
Gurdziel, Katherine
Bell, George W.
Jacks, Tyler
Flores, Elsa R.
author_sort Lin, Yu-Li
collection PubMed
description 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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spelling pubmed-27521892009-10-09 p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair Lin, Yu-Li Sengupta, Shomit Gurdziel, Katherine Bell, George W. Jacks, Tyler Flores, Elsa R. PLoS Genet Research Article 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. Public Library of Science 2009-10-09 /pmc/articles/PMC2752189/ /pubmed/19816568 http://dx.doi.org/10.1371/journal.pgen.1000680 Text en Lin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lin, Yu-Li
Sengupta, Shomit
Gurdziel, Katherine
Bell, George W.
Jacks, Tyler
Flores, Elsa R.
p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair
title p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair
title_full p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair
title_fullStr p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair
title_full_unstemmed p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair
title_short p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair
title_sort p63 and p73 transcriptionally regulate genes involved in dna repair
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752189/
https://www.ncbi.nlm.nih.gov/pubmed/19816568
http://dx.doi.org/10.1371/journal.pgen.1000680
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