Identification of four highly conserved regions in DNA-PKcs.
The gene for the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is responsible for severe combined immune deficiency (SCID) and its products associate with Ku70/Ku86 autoantigens, c-Abl, and other factors to exert its roles. Investigations to date suggest that DNA-PKcs comprises several regions which specifically interact with these known and other as yet unidentified factors. Nevertheless, the relationship between the structure and function of the DNA-PKcs molecule is poorly understood. Here we report cloning of the entire DNA-PKcs cDNA from chicken and Xenopus laevis. Comparative study of the DNA-PKcs polypeptides from four different vertebrates revealed at least three novel conserved regions in addition to the carboxyl-terminal region containing the phosphatidylinositol-3 kinase domain. We also demonstrated that the four vertebrates share the common genomic organization between a licensing factor, MCM4, and DNA-PKcs, both of which locate in a head-to-head manner within a few kilobase intervals. These data provide useful clues for the further genetic study of this huge multifunctional enzyme.
Fujimori
A
A
Department of Biology and Oncology, National Institute of Radiological Sciences, Chiba, Japan.
Araki
R
R
Fukumura
R
R
Ohhata
T
T
Takahashi
H
H
Kawahara
A
A
Tatsumi
K
K
Abe
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D002645:Chickens / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D006801:Humans; D051379:Mice; D064148:Minichromosome Maintenance Complex Component 4; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis / Q000235:genetics
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C099243:MCM4 protein, human; D064148:Minichromosome Maintenance Complex Component 4