NUCLEOTIDE-SEQUENCE ANALYSIS OF A CANDIDATE GENE FOR ATAXIA-TELANGIECTASIA GROUP-D (ATDC)

A radioresistant cell clone (1B3) was previously isolated after transf ection of an ataxia-telangiectasia (AT) group D cell line with a human cosmid library. A cosmid rescued from the integration site in 1B3 con tained human DNA from chromosome position 11q23, the same region shown by both genetic linkage and chromosome transfer to contain the genes for AT complementation groups A/B, C, and D. A gene within the cosmid (ATDC) was found to produce mRNAs of different sizes. A cDNA for one o f the most abundant mRNAs (3.0 kb) was isolated from a HeLa cell libra ry. In the present study, we sequenced the 3.0-kb cDNA and the surroun ding intron DNA in the cosmids. We used polymerase chain reaction, wit h primers in the introns, to confirm the number of exons and to analyz e DNA from AT group D cells for mutations within this gene. Although n o mutations were found, we do not rule out the possibility that mutati ons may be present within the regulatory sequences or coding sequences found in other mRNAs specific for this gene. From the sequence analys is, we found that the ATDC gene product is one of a group of proteins that share multiple zinc finger motifs and an adjacent leucine zipper motif. These proteins have been proposed to form homo- or heterodimers involved in nucleic acid binding, consistent with the fact that many of these proteins appear to be transcriptional regulatory factors invo lved in carcinogenesis and/or differentiation. The likelihood that the ATDC gene product is involved in transcriptional regulation could exp lain the pleiomorphic characteristics of AT, including abnormal cell c ycle regulation. (C) 1994 Academic Press, Inc.