Mutagenesis, Vol. 15, No. 2, 105-108,
March 2000
© 2000 UK Environmental Mutagen Society/Oxford University Press
Altered splicing of the ATDC message in ataxia telangiectasia group D cells results in the absence of a functional protein
SRI International, 333 Ravenswood Boulevard, Menlo Park, CA 94025, USA
The ATDC gene was cloned using functional complementation and complements the radiosensitivity of ataxia telangiectasia (AT) group D cells. Although a number of transcripts have been detected, only a 3.0 kb cDNA found in a HeLa cell cDNA library has been cloned. Since AT group D cells express only a 2.4 kb transcript, efforts were made to clone and sequence this transcript. Using a biotinylated oligonucleotide probe, mRNA preparations were enriched in ATDC-related sequences. After this enrichment, 2.4 kb clones were obtained from the resulting library. The 2.4 kb transcript appears to be untranslated, since no protein from this transcript has been detected in AT group D cells, and this transcript is probably non-functional, since a splicing variation has positioned part of intron 1 near the first methionine codon in exon 1, eliminating most of exon 1 and important functional regions from this transcript. This transcript now has a stop codon located 33 bp in front of the first methionine, which would stop translation after the eleventh amino acid. As a result of these changes, the AT group D cell line (AT5BI) expresses no functional ATDC protein.
1 Present address: Department of Radiation Biology RIRBM, Hiroshima University, Hiroshima 734-8553, Japan
2 To whom correspondence should be addressed at present address: Department of Ophthamology, Box 0730, University of California Medical School, San Francisco, CA 94143, USA. Tel: +1 415 476 5633; Fax: +1 415 459 4791; Email: kapp{at}cgl.ucsf.edu