Journal
SCIENCE
Volume 344, Issue 6179, Pages 55-58Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1249252
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Funding
- NSF [MCB 0718846]
- Microsoft
- NIH [GM077291]
- Fondation pour la Recherche Medicale and a Pasteur-Roux fellowship
- Maryland Stem Cell Research Fund
- National Sciences and Engineering Research Council of Canada
- U.S. Department of Energy
- JHU Applied Physics Laboratory
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1441866] Funding Source: National Science Foundation
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1443299] Funding Source: National Science Foundation
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Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MAT alpha allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.
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