Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair.
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.
Beck
Brian D
BD
Department of Biochemistry & Molecular Biology and the Walther Cancer Institute, Indiana University School of Medicine, 1044 W. Walnut Street, Indianapolis, IN 46202, USA.
Park
Su-Jung
SJ
Lee
Young-Ju
YJ
Roman
Yaritzabel
Y
Hromas
Robert A
RA
Lee
Suk-Hee
SH
D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D000072260:RNA Splicing Factors; D034741:RNA, Small Interfering / Q000235:genetics; D020079:Terminal Repeat Sequences / Q000502:physiology*
D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D034741:RNA, Small Interfering; D011495:Histone-Lysine N-Methyltransferase; C510450:SETMAR protein, human; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human