TOPORS modulates H2AX discriminating genotoxic stresses.

Ki Moon Seong, Seon Young Nam, Ji-Young Kim, Kwang Hee Yang, Sungkwan An, Young-Woo Jin, Cha Soon Kim

Division of Radiation Effect Research, Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., Ltd., 132-703, Seoul, Korea. bovine@khnp.co.kr

Journal of biochemical and molecular toxicology 2012 Nov

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H2AX plays an important role in chromatin reorganization implicated in DNA repair and apoptosis under various DNA damaging conditions. In this study, the interaction between TOPORS (topoisomerase I-binding protein) and H2AX was verified using mammalian cell extracts exposed to diverse DNA damaging stresses such as ionizing radiation, doxorubicin, camptothecin, and hydrogen peroxide. In vitro assays for ubiquitination revealed that TOPORS functions as a novel E3 ligase for H2AX ubiquitination. TOPORS was found to be dissociated from H2AX proteins when cells were exposed to oxidative stress, but not replication-inducing DNA damaging stress. The protein stability of H2AX was decreased when TOPORS was ectopically expressed in cells, and oxidative stresses such as hydrogen peroxide and ionizing radiation induced recovery of the H2AX protein level. Therefore, these biochemical data suggest that TOPORS plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. © 2012 Wiley Periodicals, Inc.

Citation

Ki Moon Seong, Seon Young Nam, Ji-Young Kim, Kwang Hee Yang, Sungkwan An, Young-Woo Jin, Cha Soon Kim. TOPORS modulates H2AX discriminating genotoxic stresses. Journal of biochemical and molecular toxicology. 2012 Nov;26(11):429-38