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J. Biol. Chem., Vol. 283, Issue 14, 9023-9030, April 4, 2008

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Human Pso4 Is a Metnase (SETMAR)-binding Partner That Regulates Metnase Function in DNA Repair^*

Brian D. Beck, Su-Jung Park, Young-Ju Lee, Yaritzabel Roman, Robert A. Hromas^¶, and Suk-Hee Lee¹

From the Department of Biochemistry & Molecular Biology and the Walther Cancer Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202 and the ^¶Department of Internal Medicine and the Cancer Treatment and Research Center, University of New Mexico, Albuquerque, New Mexico 87131

Metnase, also known as SETMAR, is a SET and transposase fusion protein with an undefined role in mammalian DNA repair. The SET domain is responsible for histone lysine methyltransferase activity at histone 3 K4 and K36, whereas the transposase domain possesses 5'-terminal inverted repeat (TIR)-specific DNA binding, DNA looping, and DNA cleavage activities. Although the transposase domain is essential for Metnase function in DNA repair, it is not clear how a protein with sequence-specific DNA binding activity plays a role in DNA repair. Here, we show that human homolog of the ScPSO4/PRP19 (hPso4) forms a stable complex with Metnase on both TIR and non-TIR DNA. The transposase domain essential for Metnase-TIR interaction is not sufficient for its interaction with non-TIR DNA in the presence of hPso4. In vivo, hPso4 is induced and co-localized with Metnase following ionizing radiation treatment. Cells treated with hPso4-siRNA failed to show Metnase localization at DSB sites and Metnase-mediated stimulation of DNA end joining coupled to genomic integration, suggesting that hPso4 is necessary to bring Metnase to the DSB sites for its function(s) in DNA repair.

Received for publication, January 7, 2008 , and in revised form, February 6, 2008.

^* This work was supported by National Institutes of Health Grant CA92111 (to S.-H. L.), National Institutes of Health Predoctoral Training Grants T32 DK0075-20 (to B. D. B.) and T32 CA111198-01 (to Y. R.), United StatesArmy Grant DAMD17-00-1-0295 (to S.-H. L.), and funds from the Walther Cancer Institute and the IU Simon Cancer Center. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: 1044 W. Walnut St., IU Cancer Research Institute, Rm. 153, Indianapolis, IN 46202. Fax: 317-274-8046; E-mail: slee{at}iupui.edu.

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This article has been cited by other articles:

				E. A. Williamson, K. K. Rasila, L. K. Corwin, J. Wray, B. D. Beck, V. Severns, C. Mobarak, S.-H. Lee, J. A. Nickoloff, and R. Hromas The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation Nucleic Acids Res., October 1, 2008; 36(18): 5822 - 5831. [Abstract] [Full Text] [PDF]