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This Week in Cell: Mar 11, 2015

A team from the Massachusetts Institute of Technology, the Broad Institute, and elsewhere describe new culprits in lung cancer formation and metastasis found with the help of a CRISPR/Cas9-mediated gene knockout screen in mouse cells. Using a set of more than 67,400 single-guide RNAs, the researchers mutagenized a mouse cancer cell line that started out non-metastatic. Following this treatment, they transplanted the cells into immunocompromised mice to track the loss-of-function mutations that influenced lung metastases in the animals. The search led to genes targeted by 624 of the single-guide RNAs, study authors say, providing clues to the metastatic process.  

Stanford researchers propose using the African turquoise killifish as a model organism for genome-to-phenotype studies of aging and age-related disease. The team introduced integrative genomics tools for the short-lived vertebrate, together with methods for doing genome assembly and CRISPR/Cas9-based genome editing on the fish. In their proof-of-principle experiments, the study's authors developed a killifish line lacking one of the telomere subunits — an organism that quickly advances to conditions that resembled age and/or telomere problems. GenomeWeb has more on the study here

Finally, a Columbia University-led team presents a single-molecule imaging method for tracking the activity of recombinase enzymes in the Rad51/RecA family as they help match up single-stranded DNA with corresponding double-stranded DNA sequences during the process of homologous recombination. Using this fluorescence microscopy-based method, the researchers untangled new details about the process that Rad51 uses to scan stretches of double-stranded DNA in search of microhomology tracts where recombination can occur. "The use of microhomology motifs as recognition elements has crucial implications for understanding how DNA sequences are aligned during [homologous recombination]," they write.