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Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function

We designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, y...

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Autores principales: Luo, Jingchuan, Vale-Silva, Luis A., Raghavan, Adhithi R., Mercy, Guillaume, Heldrich, Jonna, Sun, Xiaoji, Li, Mingyu Kenneth, Zhang, Weimin, Agmon, Neta, Yang, Kun, Cai, Jitong, Stracquadanio, Giovanni, Thierry, Agnès, Zhao, Yu, Coelho, Camila, McCulloch, Laura H., Lauer, Stephanie, Kaback, David B., Bader, Joel S., Mitchell, Leslie A., Mozziconacci, Julien, Koszul, Romain, Hochwagen, Andreas, Boeke, Jef D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667551/
https://www.ncbi.nlm.nih.gov/pubmed/38020967
http://dx.doi.org/10.1016/j.xgen.2023.100439
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author Luo, Jingchuan
Vale-Silva, Luis A.
Raghavan, Adhithi R.
Mercy, Guillaume
Heldrich, Jonna
Sun, Xiaoji
Li, Mingyu Kenneth
Zhang, Weimin
Agmon, Neta
Yang, Kun
Cai, Jitong
Stracquadanio, Giovanni
Thierry, Agnès
Zhao, Yu
Coelho, Camila
McCulloch, Laura H.
Lauer, Stephanie
Kaback, David B.
Bader, Joel S.
Mitchell, Leslie A.
Mozziconacci, Julien
Koszul, Romain
Hochwagen, Andreas
Boeke, Jef D.
author_facet Luo, Jingchuan
Vale-Silva, Luis A.
Raghavan, Adhithi R.
Mercy, Guillaume
Heldrich, Jonna
Sun, Xiaoji
Li, Mingyu Kenneth
Zhang, Weimin
Agmon, Neta
Yang, Kun
Cai, Jitong
Stracquadanio, Giovanni
Thierry, Agnès
Zhao, Yu
Coelho, Camila
McCulloch, Laura H.
Lauer, Stephanie
Kaback, David B.
Bader, Joel S.
Mitchell, Leslie A.
Mozziconacci, Julien
Koszul, Romain
Hochwagen, Andreas
Boeke, Jef D.
author_sort Luo, Jingchuan
collection PubMed
description We designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems.
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spelling pubmed-106675512023-11-09 Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function Luo, Jingchuan Vale-Silva, Luis A. Raghavan, Adhithi R. Mercy, Guillaume Heldrich, Jonna Sun, Xiaoji Li, Mingyu Kenneth Zhang, Weimin Agmon, Neta Yang, Kun Cai, Jitong Stracquadanio, Giovanni Thierry, Agnès Zhao, Yu Coelho, Camila McCulloch, Laura H. Lauer, Stephanie Kaback, David B. Bader, Joel S. Mitchell, Leslie A. Mozziconacci, Julien Koszul, Romain Hochwagen, Andreas Boeke, Jef D. Cell Genom Article We designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems. Elsevier 2023-11-09 /pmc/articles/PMC10667551/ /pubmed/38020967 http://dx.doi.org/10.1016/j.xgen.2023.100439 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Luo, Jingchuan
Vale-Silva, Luis A.
Raghavan, Adhithi R.
Mercy, Guillaume
Heldrich, Jonna
Sun, Xiaoji
Li, Mingyu Kenneth
Zhang, Weimin
Agmon, Neta
Yang, Kun
Cai, Jitong
Stracquadanio, Giovanni
Thierry, Agnès
Zhao, Yu
Coelho, Camila
McCulloch, Laura H.
Lauer, Stephanie
Kaback, David B.
Bader, Joel S.
Mitchell, Leslie A.
Mozziconacci, Julien
Koszul, Romain
Hochwagen, Andreas
Boeke, Jef D.
Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
title Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
title_full Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
title_fullStr Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
title_full_unstemmed Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
title_short Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
title_sort synthetic chromosome fusion: effects on mitotic and meiotic genome structure and function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667551/
https://www.ncbi.nlm.nih.gov/pubmed/38020967
http://dx.doi.org/10.1016/j.xgen.2023.100439
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