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Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond

Mitchell, LA and Wang, A and Stracquadanio, G and Kuang, Z and Wang, X and Yang, K and Richardson, S and Martin, JA and Zhao, Y and Walker, R and Luo, Y and Dai, H and Dong, K and Tang, Z and Yang, Y and Cai, Y and Heguy, A and Ueberheide, B and Fenyö, D and Dai, J and Bader, JS and Boeke, JD (2017) 'Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond.' Science, 355 (6329). ISSN 0036-8075

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Abstract

© 2017, American Association for the Advancement of Science. All rights reserved. We describe design, rapid assembly, and characterization of synthetic yeast Sc2.0 chromosome VI (synVI). A mitochondrial defect in the synVI strain mapped to synonymous coding changes within PRE4 (YFR050C), encoding an essential proteasome subunit; Sc2.0 coding changes reduced Pre4 protein accumulation by half. Completing Sc2.0 specifies consolidation of 16 synthetic chromosomes into a single strain. We investigated phenotypic, transcriptional, and proteomewide consequences of Sc2.0 chromosome consolidation in poly-synthetic strains. Another "bug" was discovered through proteomic analysis, associated with alteration of the HIS2 transcription start due to transfer RNA deletion and loxPsym site insertion. Despite extensive genetic alterations across 6% of the genome, no major global changes were detected in the poly-synthetic strain "omics" analyses. This work sets the stage for completion of a designer, synthetic eukaryotic genome.

Item Type: Article
Subjects: Q Science > QA Mathematics > QA75 Electronic computers. Computer science
Q Science > QA Mathematics > QA76 Computer software
Q Science > QD Chemistry
Divisions: Faculty of Science and Health > Computer Science and Electronic Engineering, School of
Depositing User: Giovanni Stracquadanio
Date Deposited: 18 May 2017 08:48
Last Modified: 30 Jan 2019 16:20
URI: http://repository.essex.ac.uk/id/eprint/19587

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