CHARACTERIZATION OF THE 5' REGION OF THE FANCONI-ANEMIA GROUP-C (FACC) GENE

Fanconi anaemia (FA) is an autosomal recessive disease characterised b y progressive pancytopenia, chromosome instability and an increased ri sk of cancer, The Fanconi Anaemia Complementation Group C (FACC) gene is mutated in patients of complementation group C, Several different f orms of FACC mRNA that share the same. coding region have been isolate d, At least two species result from the use of alternative exons at th e 5' end and three result from the use of distinct polyadenylation sig nals, As a first step toward the characterization of this gene we have isolated the genomic clones corresponding to the 5' region, including a putative promoter and two alternate 5' exons. These exons, named -1 and -1a, were found to be separated by a small intron, with exon -1 l ocated 5' to exon -1a, Further, these exons are flanked by consensus s equences of donor sites at the 5' ends of introns, An acceptor splice site was not evident 5' of exon -1a, suggesting that exon -1 is not sp liced onto exon -1a, The sequences upstream of exons -1 and -1a have n o obvious TATA or CAAT boxes but include CC-rich sequences. Functional analysis of the sequence upstream of the putative transcription start site of both alternative exons indicates that the region upstream exo n -1 is sufficient to drive the expression of the luciferase reporter gene in CaCo-2 cells and that the transcriptional regulation of this g ene is complex.