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Beck, BD, Park, SJ, Lee, YJ, Roman, Y, Hromas, RA and Lee, SH (2008) Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair. J. Biol. Chem. 283:9023-30

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.

PubMed PMC2431028 Online version:10.1074/jbc.M800150200

Cell Line; DNA Breaks, Double-Stranded; DNA Repair/physiology; DNA Repair Enzymes/antagonists & inhibitors; DNA Repair Enzymes/genetics; DNA Repair Enzymes/metabolism; DNA-Binding Proteins/antagonists & inhibitors; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Histone-Lysine N-Methyltransferase/genetics; Histone-Lysine N-Methyltransferase/metabolism; Histones/metabolism; Humans; Nuclear Proteins/antagonists & inhibitors; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Protein Structure, Tertiary/physiology; RNA, Small Interfering/genetics; Terminal Repeat Sequences/physiology