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. 2021 Mar 25;11:646256. doi: 10.3389/fonc.2021.646256

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Copyright © 2021 Liu, Lim, Cai, Ding, Tian, Dong, Zhang, Guo, Wang, Zhou and Feng

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Working model illustrates the radiosensitizing and radioprotection effect of VPA. VPA sensitizes malignantly transformed cells while protects normal cells to IR treatment. VPA enhances the DSBs level in malignant cells and alleviates the DSBs level in normal cells through regulating HR function. RFWD3 is targeted by VPA to manipulate the ubiquitination of Rad51. VPA inhibites RFWD3 to decrease the ubiquitination of Rad51 in normal cells in response to IR-induced DSBs, protecting Rad51 from degradation, while the ubiquitination is enhanced in malignant cells.