Identification of the polypyrimidine tract binding protein-associated splicing factor.p54(nrb) complex as a candidate DNA double-strand break rejoining factor.
The biological effects of ionizing radiation are attributable, in large part, to induction of DNA double-strand breaks. We report here the identification of a new protein factor that reconstitutes efficient double-strand break rejoining when it is added to a reaction containing the five other polypeptides known to participate in the human nonhomologous end-joining pathway. The factor is a stable heteromeric complex of polypyrimidine tract-binding protein-associated splicing factor (PSF) and a 54-kDa nuclear RNA-binding protein (p54(nrb)). These polypeptides, to which a variety of functions have previously been attributed, share extensive homology, including tandem RNA recognition motif domains. The PSF.p54(nrb) complex cooperates with Ku protein to form a functional preligation complex with substrate DNA. Based on structural comparison with related proteins, we propose a model where the four RNA recognition motif domains in the heteromeric PSF.p54(nrb) complex cooperate to align separate DNA molecules.
Bladen
Catherine L
CL
Program in Gene Regulation and Cancer Biology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
Udayakumar
Durga
D
Takeda
Yoshihiko
Y
Dynan
William S
WS
D020816:Amino Acid Motifs; D034961:Antigens, Nuclear / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D000072200:Ku Autoantigen; D008954:Models, Biological; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D050810:Octamer Transcription Factors; D000072670:PTB-Associated Splicing Factor; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D000072670:PTB-Associated Splicing Factor; D016601:RNA-Binding Proteins; D038941:Polypyrimidine Tract-Binding Protein; D012313:RNA; D004247:DNA; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen