title: Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes.
abstract: Defects in the human BLM gene cause Bloom syndrome, notable for early development of tumors in a broad variety of tissues. On the basis of sequence similarity, BLM has been identified as one of the five human homologs of RecQ from Escherichia coli. Nevertheless, biochemical characterization of the BLM protein indicates far greater functional similarity to the E. coli RecG protein and there is no known RecG homolog in human cells. To explore the possibility that the shared biochemistries of BLM and RecG may represent an example of convergent evolution of cellular function where in humans BLM has evolved to fulfill the genomic stabilization role of RecG, we determined whether expression of RecG in human BLM-deficient cells could suppress established functional cellular Bloom syndrome phenotypes. We found that RecG can indeed largely suppress both the definitive elevated sister chromatid exchange phenotype and the more recently demonstrated gene cluster instability phenotype of BLM-deficient cells. In contrast, expression of RecG has no impact on either of these phenotypes in human cells with functional BLM protein. These results suggest that the combination of biochemical activities shared by RecG and BLM fill the same evolutionary niche in preserving genomic integrity without requiring exactly identical molecular mechanisms.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Killen
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Stults
authors.forename: William A
authors.initials: WA
authors.lastname: Wilson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pierce
mesh_terms: D001816:Bloom Syndrome / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D005810:Multigene Family; D010641:Phenotype; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D029968:Escherichia coli Proteins; D011993:Recombinant Fusion Proteins; C071446:RecG protein, E coli; C097151:Bloom syndrome protein; D053484:RecQ Helicases