Human RecQ5β, a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerases 3α and 3β

The RecQ helicase superfamily has been implicated in DNA repair and recombination. At least five human RecQ-related genes exist: RecQ1, BLM, WRN, RecQ4 and RecQ5. Mlutations in BLM, WRN end RecQ4 are associated with Bloom, Werner and Rothmund-Thomson syndromes, respectively, involving a predisposition to malignancies and a cellular phenotype that includes increased chromosome instability. RecQ5 is small, containing only a core part of the RecQ helicase, but three isomer transcripts code for small RecQ5 alpha (corresponding to the original RecQ5 with 410 amino acids), new large RecQ5 beta (991 amino acids) and small RecQ5 gamma (435 amino acids) proteins that contain the core helicase motifs, By determining the genomic structure, we found that the three isoforms are generated by differential splicing from the RecQ5 gene that contains at least 19 exons, Northern blot analysis using a RecQ5 beta-specific probe indicates that RecQ5 beta mRNA is expressed strongly in the testis, Immunocytochemical staining of three N-terminally tagged RecQ5 isomers expressed in 293EBNA cells showed that RecQ5 beta migrates to the nucleus and exists exclusively in the nucleoplasm, while the small RecQ5a and RecQ5 gamma proteins stay in the cytoplasm, Immunoprecipitation and an extended cytochemical experiment suggested that the nucleoplasmic RecQ5 beta, like yeast Sgs1 DNA helicase, binds to topoisomerases 3 alpha and 3 beta, but not to topoisomerase 1. These results predict that RecQ5 beta may have an important role in DNA metabolism and may also be related to a distinct genetic disease.