UMI, a novel RNF168 ubiquitin binding domain involved in the DNA damage signaling pathway.
Ubiquitination regulates important cellular processes, including the DNA damage response (DDR) and DNA repair. The complexity of the ubiquitin-mediated signals is decoded by ubiquitin receptors, which contain protein modules named ubiquitin binding domains (UBDs). We previously identified a new ubiquitin ligase, RNF168, involved in DDR and endowed with two UBDs named MIU (motif interacting with ubiquitin). Here we have provided the identification of a novel UBD, the UMI (UIM- and MIU-related UBD), present in RNF168, and characterized the interaction surface with ubiquitin, centered on two Leu residues. We have demonstrated that integrity of the UMI, in addition to the MIUs, is necessary for the proper localization of RNF168 and for ubiquitination of nuclear proteins, including histone H2A. Finally, we have shown that simultaneous inactivation of UMI and MIUs prevents the recruitment to DDR foci of the crucial downstream mediator 53BP1.
Department of DISCAFF and DFB Center, University of Piemonte Orientale A. Avogadro, 28100 Novara, Italy.
Sabrina
S
Pinato
Marco
M
Gatti
Cristina
C
Scandiuzzi
Stefano
S
Confalonieri
Lorenza
L
Penengo
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004249:DNA Damage / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007930:Leucine / Q000737:chemistry; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000071857:Tumor Suppressor p53-Binding Protein 1; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D017931:DNA Primers; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D025801:Ubiquitin; C535210:RNF168 protein, human; D044767:Ubiquitin-Protein Ligases; D007930:Leucine