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SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis

In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure, the synaptonemal complex (SC). While the SC’s overall structure is highly conserved across eukaryotes, its constituent proteins div...

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Autores principales: Billmyre, Katherine Kretovich, Kesler, Emily A., Tsuchiya, Dai, Corbin, Timothy J., Weaver, Kyle, Moran, Andrea, Yu, Zulin, Adams, Lane, Delventhal, Kym, Durnin, Michael, Davies, Owen Richard, Hawley, R. Scott
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588951/
https://www.ncbi.nlm.nih.gov/pubmed/37862414
http://dx.doi.org/10.1126/sciadv.adi1562
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author Billmyre, Katherine Kretovich
Kesler, Emily A.
Tsuchiya, Dai
Corbin, Timothy J.
Weaver, Kyle
Moran, Andrea
Yu, Zulin
Adams, Lane
Delventhal, Kym
Durnin, Michael
Davies, Owen Richard
Hawley, R. Scott
author_facet Billmyre, Katherine Kretovich
Kesler, Emily A.
Tsuchiya, Dai
Corbin, Timothy J.
Weaver, Kyle
Moran, Andrea
Yu, Zulin
Adams, Lane
Delventhal, Kym
Durnin, Michael
Davies, Owen Richard
Hawley, R. Scott
author_sort Billmyre, Katherine Kretovich
collection PubMed
description In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure, the synaptonemal complex (SC). While the SC’s overall structure is highly conserved across eukaryotes, its constituent proteins diverge between phyla. Transverse filament protein, SYCP1, spans the width of the SC and undergoes amino-terminal head-to-head self-assembly in vitro through a motif that is unusually highly conserved across kingdoms of life. Here, we report creation of mouse mutants, Sycp1(L102E) and Sycp1(L106E), that target SYCP1’s head-to-head interface. L106E resulted in a complete loss of synapsis, while L102E had no apparent effect on synapsis, in agreement with their differential effects on the SYCP1 head-to-head interface in molecular dynamics simulations. In Sycp1(L106E) mice, homologs aligned and recruited low levels of mutant SYCP1 and other SC proteins, but the absence of synapsis led to failure of crossover formation and meiotic arrest. We conclude that SYCP1’s conserved head-to-head interface is essential for meiotic chromosome synapsis in vivo.
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spelling pubmed-105889512023-10-21 SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis Billmyre, Katherine Kretovich Kesler, Emily A. Tsuchiya, Dai Corbin, Timothy J. Weaver, Kyle Moran, Andrea Yu, Zulin Adams, Lane Delventhal, Kym Durnin, Michael Davies, Owen Richard Hawley, R. Scott Sci Adv Biomedicine and Life Sciences In almost all sexually reproducing organisms, meiotic recombination and cell division require the synapsis of homologous chromosomes by a large proteinaceous structure, the synaptonemal complex (SC). While the SC’s overall structure is highly conserved across eukaryotes, its constituent proteins diverge between phyla. Transverse filament protein, SYCP1, spans the width of the SC and undergoes amino-terminal head-to-head self-assembly in vitro through a motif that is unusually highly conserved across kingdoms of life. Here, we report creation of mouse mutants, Sycp1(L102E) and Sycp1(L106E), that target SYCP1’s head-to-head interface. L106E resulted in a complete loss of synapsis, while L102E had no apparent effect on synapsis, in agreement with their differential effects on the SYCP1 head-to-head interface in molecular dynamics simulations. In Sycp1(L106E) mice, homologs aligned and recruited low levels of mutant SYCP1 and other SC proteins, but the absence of synapsis led to failure of crossover formation and meiotic arrest. We conclude that SYCP1’s conserved head-to-head interface is essential for meiotic chromosome synapsis in vivo. American Association for the Advancement of Science 2023-10-20 /pmc/articles/PMC10588951/ /pubmed/37862414 http://dx.doi.org/10.1126/sciadv.adi1562 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Billmyre, Katherine Kretovich
Kesler, Emily A.
Tsuchiya, Dai
Corbin, Timothy J.
Weaver, Kyle
Moran, Andrea
Yu, Zulin
Adams, Lane
Delventhal, Kym
Durnin, Michael
Davies, Owen Richard
Hawley, R. Scott
SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis
title SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis
title_full SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis
title_fullStr SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis
title_full_unstemmed SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis
title_short SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis
title_sort sycp1 head-to-head assembly is required for chromosome synapsis in mouse meiosis
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588951/
https://www.ncbi.nlm.nih.gov/pubmed/37862414
http://dx.doi.org/10.1126/sciadv.adi1562
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