Open AccessAn EZH2-mediated epigenetic mechanism behind p53-dependent tissue sensitivity to DNA damage
Author(s) -
Gamze Kuser Abali,
Lu Gong,
Jiawei Yan,
Qingqing Liu,
Weiqi Zeng,
Amanda K. Williamson,
Chuan Bian Lim,
Mary E. Molloy,
John B. Little,
Lei Huang,
Zhi-Min Yuan
Publication year - 2018
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1719532115
Subject(s) - mdmx , ezh2 , dna damage , chromatin , mdm2 , radiation sensitivity , epigenetics , cancer research , mechanism (biology) , dna , biology , microbiology and biotechnology , chemistry , genetics , apoptosis , gene , philosophy , irradiation , nuclear physics , epistemology , physics
Significance p53 is widely perceived as a determinant of sensitivity to radio-/chemotherapy. We report a distinct mechanism whereby p53-regulated MDM2 works together with MDMX to modulate sensitivity to DNA damage by controlling EZH2 (enhancer of zeste homolog 2) turnover. Our work uncovers a mechanism of chromatin modification underlying tissue sensitivity to DNA damage. The MDM2/MDMX disruptor can be used for protecting renewable tissues from chemo-/radiotherapy-induced damage, and the EZH2 inhibitor for sensitizing p53-mutant cancer cells to chemo-/radiotherapy.
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