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Total synthesis of a functional designer eukaryotic chromosome.

Narayana Annaluru ¹ Héloïse Muller ^{2, 1, 3} Leslie A. Mitchell ⁴ Sivaprakash Ramalingam ⁵ Giovanni Stracquadanio ^{3, 6} Sarah M Richardson ⁶ Jessica S. Dymond ⁷ Zheng Kuang ³ Lisa Z. Scheifele ^{3, 8} Eric M. Cooper ³ Yizhi Cai ^{9, 10} Karen Zeller ³ Neta Agmon ^{3, 4} Jeffrey S. Han ¹¹ Michalis Hadjithomas ¹² Jennifer Tullman ⁶ Katrina Caravelli ^{3, 13} Kimberly Cirelli ^{1, 13} Zheyuan Guo ^{1, 14} Viktoriya London ^{1, 14} Apurva Yeluru ^{1, 14} Sindurathy Murugan ⁶ Karthikeyan Kandavelou ^{1, 15} Nicolas Agier ¹⁶ Gilles Fischer ¹⁶ Kun Yang ^{3, 6} J. Andrew Martin ^{3, 6} Murat Bilgel ¹⁴ Pavlo Bohutskyi ¹⁴ Kristin M. Boulier ¹³ Brian J. Capaldo ¹⁴ Joy Chang ¹⁴ Kristie Charoen ¹⁴ Woo Jin Choi ¹⁴ Peter Deng ¹² James E Dicarlo ¹⁴ Judy Doong ¹⁴ Jessilyn Dunn ¹⁴ Jason I Feinberg ¹³ Christopher Fernandez ¹³ Charlotte E Floria ¹³ David Gladowski ¹³ Pasha Hadidi ¹⁴ Isabel Ishizuka ¹³ Javaneh Jabbari ¹³ Calvin Y. L. Lau ¹⁴ Pablo A. Lee ¹⁴ Sean Li ¹⁴ Denise Lin ¹³ Matthias E. Linder ¹³ Jonathan Ling ¹⁴ Jaime Liu ¹⁴ Jonathan Liu ¹⁴ Mariya London ¹³ Henry Ma ¹⁴ Jessica Mao ¹⁴ Jessica E Mcdade ¹⁴ Alex Mcmillan ¹³ Aaron M Moore ¹³ Won Chan Oh ¹⁴ Yu Ouyang ¹⁴ Ruchi Patel ¹⁴ Marina Paul ¹³ Laura C Paulsen ¹⁴ Judy Qiu ¹⁴ Alex Rhee ¹⁴ Matthew G Rubashkin ¹⁴ Ina Y. Soh ¹³ Nathaniel E Sotuyo ¹³ Venkatesh Srinivas ¹⁴ Allison Suarez ¹⁴ Andy Wong ¹⁴ Remus Wong ¹⁴ Wei Rose Xie ¹³ Yijie Xu ¹⁴ Allen T Yu ¹³ Romain Koszul ² Joel S. Bader ^{3, 6} Jef D Boeke ^{3, 4, 12} Srinivasan Chandrasegaran ¹

1 Department of Environmental Health Sciences [JHU Baltimore]

2 Régulation spatiale des Génomes - Spatial Regulation of Genomes

3 High Throughput Biology Center [Baltimore]

4 NYU Langone Medical Center - New York University Langone Medical Center

5 JHU - Johns Hopkins University

6 Department of Biomedical Engineering and Institute of Genetic Medicine, Whiting School of Engineering

7 Biological Sciences, Research and Exploratory Development Department [Laurel]

8 Department of Biology [Loloya U. Baltimore]

9 Johns Hopkins University School of Medicine [Baltimore]

10 University of Edinburgh

11 Carnegie Institution for Science

12 Department of Biology [JHU Baltimore]

13 Krieger School of Arts and Sciences [Baltimore]

14 Whiting School of Engineering [Baltimore]

15 Pondicherry Biotech Private Limited

16 LGM - Génomique des Microorganismes

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, 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 MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Biochemistry, Molecular Biology / Molecular biology

Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-01420002
Contributor : Romain Koszul Connect in order to contact the contributor
Submitted on : Tuesday, December 20, 2016 - 11:44:58 AM
Last modification on : Monday, September 12, 2022 - 10:40:17 PM