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TOPORS Modulates H2AX Discriminating Genotoxic Stresses
Author(s) -
Seong Ki Moon,
Nam Seon Young,
Kim JiYoung,
Yang Kwang Hee,
An Sungkwan,
Jin YoungWoo,
Kim Cha Soon
Publication year - 2012
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21438
Subject(s) - dna damage , chromatin , topoisomerase , ubiquitin , camptothecin , oxidative stress , dna , chemistry , microbiology and biotechnology , ubiquitin ligase , dna repair , dna ligase , biology , biochemistry , gene
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. J Biochem Mol Toxicol 26:429‐438, 2012; View this article online at wileyonlinelibrary.com . DOI 10:1002/jbt.21438