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.
Highlights
Human cells possess five proteins with clear sequence homology to the E. coli RecQ protein: BLM, WRN, RECQL, RECQL4 and RECQL5
RecG fusion proteins in E. coli largely retain functionality [43], and the RecG-enhanced green fluorescent protein (EGFP) fusion protein plasmid used in this work increases the resistance of deletion recG E. coli to mitomycin C (Robert Lloyd, personal communication)
The capacity with which RecG can suppress BLM- cellular phenotypes suggests that the physiological role of BLM in suppressing the two phenotype we investigated, sister chromatid exchanges and gene cluster instability, is to perform the same molecular reactions that can be performed in a human cell by the RecG monomer alone, namely direct manipulations of DNA structures
Summary
Human cells possess five proteins with clear sequence homology to the E. coli RecQ protein: BLM, WRN, RECQL, RECQL4 and RECQL5. These proteins are all implicated in preserving genomic integrity (reviewed in [1,2]). Sequence homology of BLM with RecQ notwithstanding, characterization of the in vitro activities of BLM demonstrates significant similarities to the biochemistry of the E. coli RecG DNA translocase protein. Both BLM [4,5] and RecG [6,7] can bind to and regress multistranded DNA structures that model stalled replication. We assayed the resulting RecG transgene expressing cells for changes in these two phenotypes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
