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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2010
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| Online Access: | http://hdl.handle.net/1721.1/52572 https://orcid.org/0000-0001-5785-8911 |
| _version_ | 1826196585981149184 |
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| author | Lin, Yu-Li Sengupta, Shomit Gurdziel, Katherine Bell, George W. Flores, Elsa R. Jacks, Tyler E |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Lin, Yu-Li Sengupta, Shomit Gurdziel, Katherine Bell, George W. Flores, Elsa R. Jacks, Tyler E |
| author_sort | Lin, Yu-Li |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T10:29:33Z |
| format | Article |
| id | mit-1721.1/52572 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:29:33Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
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| spelling | mit-1721.1/525722022-09-30T21:28:58Z p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair Lin, Yu-Li Sengupta, Shomit Gurdziel, Katherine Bell, George W. Flores, Elsa R. Jacks, Tyler E Broad Institute of MIT and Harvard Koch Institute for Integrative Cancer Research at MIT Jacks, Tyler E. Sengupta, Shomit Gurdziel, Katherine Jacks, Tyler E. 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. 2010-03-15T13:31:12Z 2010-03-15T13:31:12Z 2009-10 2009-04 Article http://purl.org/eprint/type/JournalArticle 1553-7390 1553-7404 http://hdl.handle.net/1721.1/52572 Lin Y-L, Sengupta S, Gurdziel K, Bell GW, Jacks T, et al. (2009) p63 and p73 Transcriptionally Regulate Genes Involved in DNA Repair. PLoS Genet 5(10): e1000680. doi:10.1371/journal.pgen.1000680 19816568 https://orcid.org/0000-0001-5785-8911 en_US http://dx.doi.org/10.1371/journal.pgen.1000680 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Lin, Yu-Li Sengupta, Shomit Gurdziel, Katherine Bell, George W. Flores, Elsa R. Jacks, Tyler E 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 |
| url | http://hdl.handle.net/1721.1/52572 https://orcid.org/0000-0001-5785-8911 |
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