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The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging

Author

Listed:
  • Chun Zhou

    (International Cancer Center of Shenzhen University
    BGI Research
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yun Wang

    (BGI Research
    BGI Research)

  • Yikun Huang

    (International Cancer Center of Shenzhen University)

  • Yongpan An

    (Peking University)

  • Xian Fu

    (BGI Research
    BGI Research)

  • Daqian Yang

    (Peking University)

  • Yilin Wang

    (International Cancer Center of Shenzhen University)

  • Jintao Zhang

    (BGI Research)

  • Leslie A. Mitchell

    (NYU Langone Health
    Inc.)

  • Joel S. Bader

    (Johns Hopkins University)

  • Yizhi Cai

    (131 Princess Street)

  • Junbiao Dai

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Agricultural Sciences)

  • Jef D. Boeke

    (NYU Langone Health
    NYU Tandon School of Engineering)

  • Zhiming Cai

    (International Cancer Center of Shenzhen University
    Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors)

  • Zhengwei Xie

    (Peking University)

  • Yue Shen

    (BGI Research
    University of Chinese Academy of Sciences
    BGI Research)

  • Weiren Huang

    (International Cancer Center of Shenzhen University
    Chinese Academy of Sciences
    Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors
    Guangdong Engineering Technology Research Center for clinical application of cancer genome)

Abstract

In the era of synthetic biology, design, construction, and utilization of synthetic chromosomes with unique features provide a strategy to study complex cellular processes such as aging. Herein, we successfully construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging using these synthetic strains. We verify that up-regulation of a rRNA-related transcriptional factor, RRN9, positively influence replicative lifespan. Using SCRaMbLE system that enables inducible whole-genome rearrangement on synXIII, we obtain 20 SCRaMbLEd synXIII strains with extended lifespan. Transcriptome analysis reveal the expression of genes involve in global protein synthesis is up-regulated in longer-lived strains. We establish causal links between genotypic change and the long-lived phenotype via reconstruction of some key structural variations observed in post-SCRaMbLE strains and further demonstrate combinatorial effects of multiple aging regulators on lifespan extension. Our findings underscore the potential of synthetic yeasts in unveiling the function of aging-related genes.

Suggested Citation

  • Chun Zhou & Yun Wang & Yikun Huang & Yongpan An & Xian Fu & Daqian Yang & Yilin Wang & Jintao Zhang & Leslie A. Mitchell & Joel S. Bader & Yizhi Cai & Junbiao Dai & Jef D. Boeke & Zhiming Cai & Zhengw, 2024. "The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54130-3
    DOI: 10.1038/s41467-024-54130-3
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    References listed on IDEAS

    as
    1. Michael J. Shen & Yi Wu & Kun Yang & Yunxiang Li & Hui Xu & Haoran Zhang & Bing-Zhi Li & Xia Li & Wen-Hai Xiao & Xiao Zhou & Leslie A. Mitchell & Joel S. Bader & Yingjin Yuan & Jef D. Boeke, 2018. "Heterozygous diploid and interspecies SCRaMbLEing," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
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