{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kuser-Abali G"],"funding":["NIH/NCI","NCI NIH HHS"],"pagination":["3452-3457"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5879692"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["115(13)"],"pubmed_abstract":["Renewable tissues exhibit heightened sensitivity to DNA damage, which is thought to result from a high level of p53. However, cell proliferation in renewable tissues requires p53 down-regulation, creating an apparent discrepancy between the p53 level and elevated sensitivity to DNA damage. Using a combination of genetic mouse models and pharmacologic inhibitors, we demonstrate that it is p53-regulated MDM2 that functions together with MDMX to regulate DNA damage sensitivity by targeting EZH2 (enhancer of zeste homolog 2) for ubiquitination/degradation. As a methyltransferase, EZH2 promotes H3K27me3, and therefore chromatin compaction, to determine sensitivity to DNA damage. We demonstrate that genetic and pharmacologic interference of the association between MDM2 and MDMX stabilizes EZH2, "],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["An EZH2-mediated epigenetic mechanism behind p53-dependent tissue sensitivity to DNA damage."],"pmcid":["PMC5879692"],"funding_grant_id":["R01CA125144","R01CA85679","R01 CA125144","R01CA167814","R01 CA085679","R01 CA167814"],"pubmed_authors":["Yuan ZM","Yan J","Little JB","Lim CB","Williamson A","Liu Q","Gong L","Molloy ME","Huang L","Kuser-Abali G","Zeng W"],"additional_accession":[]},"is_claimable":false,"name":"An EZH2-mediated epigenetic mechanism behind p53-dependent tissue sensitivity to DNA damage.","description":"Renewable tissues exhibit heightened sensitivity to DNA damage, which is thought to result from a high level of p53. However, cell proliferation in renewable tissues requires p53 down-regulation, creating an apparent discrepancy between the p53 level and elevated sensitivity to DNA damage. Using a combination of genetic mouse models and pharmacologic inhibitors, we demonstrate that it is p53-regulated MDM2 that functions together with MDMX to regulate DNA damage sensitivity by targeting EZH2 (enhancer of zeste homolog 2) for ubiquitination/degradation. As a methyltransferase, EZH2 promotes H3K27me3, and therefore chromatin compaction, to determine sensitivity to DNA damage. We demonstrate that genetic and pharmacologic interference of the association between MDM2 and MDMX stabilizes EZH2, ","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Mar","modification":"2026-05-05T21:22:54.372Z","creation":"2019-03-26T23:57:06Z"},"accession":"S-EPMC5879692","cross_references":{"pubmed":["29540569"],"doi":["10.1073/pnas.1719532115"]}}