Drosophila and human RecQ5 exist in different isoforms generated by alternative splicing

Members of the RecQ helicase superfamily have been implicated in DNA repair , recombination and replication. Although the genome of the budding yeast S accharomyces cerevisiae encodes only a single member of this family, there are at least five human RecQ-related genes: RecQL, BLM, WRN, RecQ4 and RecQ 5, Mutations in at least three of these are associated with diseases involv ing a predisposition to malignancies and a cellular phenotype that includes increased chromosome instability, Metazoan RecQ helicases are defined by a core region with characteristic helicase motifs and sequence similarity to Escherichia coli RecQ protein. This core region is typically flanked by ex tensive, highly charged regions, of largely unknown function. The recently reported human RecQ5, however, has only the core RecQ-homologous region. We describe here the identification of the Drosophila RecQ5 gene. We recovere d cDNAs corresponding to three alternative splice forms of the RecQ5 transc ript. Two of these generate nearly identical 54 kDa proteins that, like hum an RecQ5, consist of the helicase core only. The third splice variant encod es a 121 kDa isoform that, like other family members, has a C-terminal exte nsion rich in charged residues. A combination of RACE and cDNA analysis of human RECQ5 demonstrates extensive alternative splicing for this gene also, including some forms lacking helicase motifs and other conserved regions.