학술논문
Total Synthesis of a Functional Designer Eukaryotic Chromosome
Document Type
research-article
Author
Annaluru, Narayana; Muller, Héloïse; Mitchell, Leslie A.; Ramalingam, Sivaprakash; Stracquadanio, Giovanni; Richardson, Sarah M.; Dymond, Jessica S.; Kuang, Zheng; Scheifele, Lisa Z.; Cooper, Eric M.; Cai, Yizhi; Zeller, Karen; Agmon, Neta; Han, Jeffrey S.; Hadjithomas, Michalis; Tullman, Jennifer; Caravelli, Katrina; Cirelli, Kimberly; Guo, Zheyuan; London, Viktoriya; Yeluru, Apurva; Murugan, Sindurathy; Kandavelou, Karthikeyan; Agier, Nicolas; Fischer, Gilles; Yang, Kun; Martin, Andrew; Bilgel, Murat; Bohutski, Pavlo; Boulier, Kristin M.; Capaldo, Brian J.; Chang, Joy; Charoen, Kristie; Choi, Woo Jin; Deng, Peter; DiCarlo, James E.; Doong, Judy; Dunn, Jessilyn; Feinberg, Jason I.; Fernandez, Christopher; Floria, Charlotte E.; Gladowski, David; Hadidi, Pasha; Ishizuka, Isabel; Jabbari, Javaneh; Lau, Calvin Y. L.; Lee, Pablo A.; Li, Sean; Lin, Denise; Linder, Matthias E.; Ling, Jonathan; Liu, Jaime; Liu, Jonathan; London, Mariya; Ma, Henry; Mao, Jessica; McDade, Jessica E.; McMillan, Alexandra; Moore, Aaron M.; Oh, Won Chan; Ouyang, Yu; Patel, Ruchi; Paul, Marina; Paulsen, Laura C.; Qiu, Judy; Rhee, Alex; Rubashkin, Matthew G.; Soh, Ina Y.; Sotuyo, Nathaniel E.; Srinivas, Venkatesh; Suarez, Allison; Wong, Andy; Wong, Remus; Xie, Wei Rose; Xu, Yijie; Yu, Allen T.; Koszul, Romain; Bader, Joel S.; Boeke, Jef D.; Chandrasegaran, Srinivasan
Source
Science, 2014 Apr 01. 344(6179), 55-58.
Subject
Language
English
ISSN
00368075
10959203
10959203
Abstract
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, synlll, 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 MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.