RPAP3 interacts with Reptin to regulate UV‐induced phosphorylation of H2AX and DNA damage |
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| Authors: | Lin Ni Makio Saeki Li Xu Hirokazu Nakahara Masafumi Saijo Kiyoji Tanaka Yoshinori Kamisaki |
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| Institution: | 1. Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan;2. Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Beijing, China;3. The First Department of Oral & Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan;4. Laboratories for Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan;5. Solution Oriented Research for Science and Technology of Japan Science and Technology Agency, Kawaguchi, Saitama, Japan;6. E‐Institute of Shanghai Universities, Division of Nitric Oxide and Inflammatory Medicine, Shanghai, China |
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| Abstract: | We have previously reported that Monad, a novel WD40 repeat protein, potentiates apoptosis induced by tumor necrosis factor‐α and cycloheximide. By affinity purification and mass spectrometry, RNA polymerase II‐associated protein 3 (RPAP3) was identified as a Monad binding protein and may function with Monad as a novel modulator of apoptosis pathways. Here we report that Reptin, a highly conserved AAA + ATPase that is part of various chromatin‐remodeling complexes, is also involved in the association of RPAP3 by immunoprecipitation and confocal microscopic analysis. Overexpression of RPAP3 induced HEK293 cells to death after UV‐irradiation. Loss of RPAP3 by RNAi improved HeLa cell survival after UV‐induced DNA damage and attenuated the phosphorylation of H2AX. Depletion of Reptin reduced cell survival and facilitated the phosphorylation on H2AX. These results suggest that RPAP3 modulates UV‐induced DNA damage by regulating H2AX phosphorylation. J. Cell. Biochem. 106: 920–928, 2009. © 2009 Wiley‐Liss, Inc. |
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| Keywords: | RPAP3 Monad Reptin H2AX UV chromatin remodeling |
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