Rosa26-GFP Direct Repeat (RaDR-GFP) Mice Reveal Tissue- and Age-Dependence of Homologous Recombination in Mammals


Cancer is a disease of the genome, caused by accumulated genetic changes, such as point mutations and large-scale sequence rearrangements. Homologous recombination (HR) is a critical DNA repair pathway. While generally accurate, HR between misaligned sequences or between homologous chromosomes can lead to insertions, deletions, and loss of heterozygosity, all of which are known to promote cancer. Indeed, most cancers harbor sequence changes caused by HR, and genetic and environmental conditions that induce or suppress HR are often carcinogenic. To enable studies of HR in vivo, we created the Rosa26 Direct Repeat-Green Fluorescent Protein (RaDR-GFP) mice that carry an integrated transgenic recombination reporter targeted to the ubiquitously expressed Rosa26 locus. Being able to detect recombinant cells by fluorescence reveals that the frequency of recombination is highly variable among tissues. Furthermore, new recombination events accumulate over time, which contributes to our understanding of why our risk for cancer increases with age. This mouse model provides new understanding of this important DNA repair pathway in vivo, and also enables future studies of genetic, environmental and physiological factors that impact the risk of HR-induced sequence rearrangements in vivo.


Vyšlo v časopise: Rosa26-GFP Direct Repeat (RaDR-GFP) Mice Reveal Tissue- and Age-Dependence of Homologous Recombination in Mammals. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004299
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004299

Souhrn

Cancer is a disease of the genome, caused by accumulated genetic changes, such as point mutations and large-scale sequence rearrangements. Homologous recombination (HR) is a critical DNA repair pathway. While generally accurate, HR between misaligned sequences or between homologous chromosomes can lead to insertions, deletions, and loss of heterozygosity, all of which are known to promote cancer. Indeed, most cancers harbor sequence changes caused by HR, and genetic and environmental conditions that induce or suppress HR are often carcinogenic. To enable studies of HR in vivo, we created the Rosa26 Direct Repeat-Green Fluorescent Protein (RaDR-GFP) mice that carry an integrated transgenic recombination reporter targeted to the ubiquitously expressed Rosa26 locus. Being able to detect recombinant cells by fluorescence reveals that the frequency of recombination is highly variable among tissues. Furthermore, new recombination events accumulate over time, which contributes to our understanding of why our risk for cancer increases with age. This mouse model provides new understanding of this important DNA repair pathway in vivo, and also enables future studies of genetic, environmental and physiological factors that impact the risk of HR-induced sequence rearrangements in vivo.


Zdroje

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