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Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes

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 B...

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Autores principales: Killen, Michael W, Stults, Dawn M, Wilson, William A, Pierce, Andrew J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517418/
https://www.ncbi.nlm.nih.gov/pubmed/23110454
http://dx.doi.org/10.1186/1471-2199-13-33
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author Killen, Michael W
Stults, Dawn M
Wilson, William A
Pierce, Andrew J
author_facet Killen, Michael W
Stults, Dawn M
Wilson, William A
Pierce, Andrew J
author_sort Killen, Michael W
collection PubMed
description 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.
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spelling pubmed-35174182012-12-08 Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes Killen, Michael W Stults, Dawn M Wilson, William A Pierce, Andrew J BMC Mol Biol Research Article 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. BioMed Central 2012-10-30 /pmc/articles/PMC3517418/ /pubmed/23110454 http://dx.doi.org/10.1186/1471-2199-13-33 Text en Copyright ©2012 Killen et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Killen, Michael W
Stults, Dawn M
Wilson, William A
Pierce, Andrew J
Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes
title Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes
title_full Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes
title_fullStr Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes
title_full_unstemmed Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes
title_short Escherichia coli RecG functionally suppresses human Bloom syndrome phenotypes
title_sort escherichia coli recg functionally suppresses human bloom syndrome phenotypes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517418/
https://www.ncbi.nlm.nih.gov/pubmed/23110454
http://dx.doi.org/10.1186/1471-2199-13-33
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