GENOMIC STRUCTURE AND CHROMOSOMAL ASSIGNMENT OF THE MOUSE KU70 GENE

DNA-dependent protein kinase (DNA-PK) consists of three polypeptide su bunits: Ku70, Ku80, and the DNA-Pk catalytic subunit (DNA-PKcs). Mamma lian mutants deficient in either Ku80 or DNA-PHcs function have been s hown to be lacking in DNA double-strand break repair and V(D)J recombi nation, respectively. The precise role of the Ku70 gene in this proces s has not yet been determined, in part because no cell lines, animals, or human diseases involved with deficiencies in this gene have yet be en identified. Both the human and the mouse Ku70 cDNAs have been clone d, and the human gene has been mapped to chromosome 22q13. The origina l mouse cDNA clones, however, lacked a complete 5'-region, and none of the mammalian Ku70 genomic sequences have been characterized. This re port contains an analysis of the 5'-region of the mouse cDNA sequence, a characterization of the mouse Ku70 genomic structure, and fluoresce nce in situ hybridization data that map the mouse gene to chromosome 1 5. The deduced amino acid sequence of the mouse gene consists of 608 a mino acids compared to 609 for the human gene. The genomic sequence is 24 kb and consists of 13 exons, including an untranslated first exon. Sequences from the upstream region of exon 1 revealed four consensus GC box sequences and a strong transcription initiation site at a reaso nable location. The assignment of the mouse Ku70 gene to chromosome 15 is consistent with the syntenic relationship of this gene in human (c hromosome 22q13) and mouse and adds to the comparative mapping data fo r the genes involved in the SCID phenotype. (C) 1996 Academic Press, I nc.