Complete sequencing of full-length canine ataxia telangiectasia mutated mRNA and characterization of its putative promoter.
Ataxia telangiectasia mutated (ATM) protein is considered a "caretaker" of the genome integrity and a defective ATM has been correlated with increased cancer risk in human beings. In an effort to explore the reliability of dog as a spontaneous animal model of genetic susceptibility to lymphoid malignancies, we have carried out the complete sequencing of the canine ATM mRNA. 5' RACE analysis and sequencing were used to obtain the full-length canine cDNA. The transcription start site was found at CFA5: 27307661 (Dog Genome assembly 2.0, release 49). Two exons were found in the 5'UTR. A putative TATA-less bi-directional promoter region was found in the region 5' upstream of the cap site. The core promoter harbours different conserved regulatory motifs: CREB, CCAAT boxes (NF-binding sites), Sp1, AP-2, GCF, XRE, Ets, Cre and c-Myb. The major ORF, corresponding to the ortholog human and pig ATM isoform 1, has 64 exons and codes a protein of 3056 aa. The homology between dog and human ATM at the aa level was 89% identities-93% positives, even higher than the homology between pig and human. When compared with the canine genomic sequences, 3 sequence variants yielding to aa substitution were found. Canine ATM is highly conserved and may represent a candidate gene to evaluate lymphoid malignancies predisposition in dogs.
Gentilini
Fabio
F
Veterinary Clinical Department, Alma Mater Studiorum-University of Bologna, Bologna, Italy. fabio.gentilini@unibo.it
Turba
Maria Elena
ME
Forni
Monica
M
Cinotti
Stefano
S
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D004285:Dogs / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000276:immunology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases