CAND3 - A UBIQUITOUSLY EXPRESSED GENE IMMEDIATELY ADJACENT AND IN OPPOSITE TRANSCRIPTIONAL ORIENTATION TO THE ATM GENE AT 11Q23.1

Using a magnetic beads-mediated cDNA selection procedure and a fetal b rain expression library, we identified a transcriptional unit within a cosmid positive for the marker D11S384. Pursuit of its full-length cD NA led to the cloning of the third candidate gene (CAND3) we studied i n our quest for the ataxiatelangiectasia (A-T) gene, ATM. CAND3 spans similar to 140 kb of genomic DNA and is located immediately centrimeri c to ATM, with 544 bp of DNA separating the two genes. CAND3 encodes t wo ubiquitously expressed transcripts of similar to 5.8 kb and similar to 4.6 kb that are divergently transcribed from a promoter region com mon to ATM. Nucleotide sequence was determined for one of its alternat ely spliced transcripts. The predicted protein has 1175 amino acids an d is novel in sequence, with only weak homologies to transcriptional f actors, nucleoporin protein, and protein kinases, including members of the phosphatidylinositol 3-kinase (PI-3 kinase) family. Although neit her homology to ATM nor any mutation of CAND3 in A-T patients has been found, the head-to-head arrangement of CAND3 and ATM, with expression of both housekeeping genes from a common stretch of 544 bp intergenic DNA, suggests a bi-directional promoter possibly for co-regulation of biologically related functions. YACs, BACs, cosmids, and STSs are def ined to aid in the further study of this gene.