Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics

Resolution of chromosome bridges during mitosis is a critical yet incompletely understood process with implications for genomic stability and cancer development. In this study, we investigated the impact of the bridging chromatin length on the timing and mechanism of chromosome bridge resolution. Us...

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Autores: Anglada Pons, Teresa|||0000-0002-2441-4262, Rodriguez Muñoz, Marina|||0000-0002-1658-2493, Pulido-Artola, Núria|||0009-0001-6252-4737, Genescà, Anna|||0000-0002-0509-956X
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311916
Acceso en línea:https://ddd.uab.cat/record/311916
https://dx.doi.org/urn:doi:10.1096/fj.202402258RR
Access Level:acceso abierto
Palabra clave:Bridging chromatin length
Chromosome bridge
CRISPR/Cas9
Mitosis
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spelling Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution DynamicsAnglada Pons, Teresa|||0000-0002-2441-4262Rodriguez Muñoz, Marina|||0000-0002-1658-2493Pulido-Artola, Núria|||0009-0001-6252-4737Genescà, Anna|||0000-0002-0509-956XBridging chromatin lengthChromosome bridgeCRISPR/Cas9MitosisResolution of chromosome bridges during mitosis is a critical yet incompletely understood process with implications for genomic stability and cancer development. In this study, we investigated the impact of the bridging chromatin length on the timing and mechanism of chromosome bridge resolution. Using CRISPR/Cas9 technology, we engineered chromosome bridges with precisely defined intercentromeric distances in human RPE-1 cells. Our study revealed a decline in the frequency of chromosome bridges as cells progressed from early anaphase to late telophase, indicating resolution during mitosis. Moreover, the longer the bridging chromatin length, the higher the frequency of chromosome bridges observed at the mitotic exit, demonstrating that the size of the bridge influences its resolution during mitosis. Additionally, the separation between the bridge kinetochores needed for bridge breakage was strongly dependent on the megabase length of the bridging chromatin, with longer chromosome bridges requiring greater separation for their resolution. Given that chromosome bridge resolution occurs in a concerted manner with spindle elongation and is influenced by the length of the bridging chromatin, we posit that the traction forces generated by microtubules attaching to dicentric chromosomes play a significant role in resolving chromosome bridges during mitosis. Our study underscores the intricate interplay between chromosome bridge geometry and mechanical forces in mitotic chromosome bridge resolution. Our model offers a valuable framework for future investigations into the molecular mechanisms underlying chromosome bridge resolution, with potential implications for cancer biology and genomic stability maintenance. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/311916https://dx.doi.org/urn:doi:10.1096/fj.202402258RRreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2021/SGR-122open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3119162026-06-06T12:50:31Z
dc.title.none.fl_str_mv Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
title Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
spellingShingle Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
Anglada Pons, Teresa|||0000-0002-2441-4262
Bridging chromatin length
Chromosome bridge
CRISPR/Cas9
Mitosis
title_short Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
title_full Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
title_fullStr Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
title_full_unstemmed Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
title_sort Engineering Chromosome Bridges Through CRISPR/Cas9 to Decipher the Impact of Intercentromeric Distance on Resolution Dynamics
dc.creator.none.fl_str_mv Anglada Pons, Teresa|||0000-0002-2441-4262
Rodriguez Muñoz, Marina|||0000-0002-1658-2493
Pulido-Artola, Núria|||0009-0001-6252-4737
Genescà, Anna|||0000-0002-0509-956X
author Anglada Pons, Teresa|||0000-0002-2441-4262
author_facet Anglada Pons, Teresa|||0000-0002-2441-4262
Rodriguez Muñoz, Marina|||0000-0002-1658-2493
Pulido-Artola, Núria|||0009-0001-6252-4737
Genescà, Anna|||0000-0002-0509-956X
author_role author
author2 Rodriguez Muñoz, Marina|||0000-0002-1658-2493
Pulido-Artola, Núria|||0009-0001-6252-4737
Genescà, Anna|||0000-0002-0509-956X
author2_role author
author
author
dc.subject.none.fl_str_mv Bridging chromatin length
Chromosome bridge
CRISPR/Cas9
Mitosis
topic Bridging chromatin length
Chromosome bridge
CRISPR/Cas9
Mitosis
description Resolution of chromosome bridges during mitosis is a critical yet incompletely understood process with implications for genomic stability and cancer development. In this study, we investigated the impact of the bridging chromatin length on the timing and mechanism of chromosome bridge resolution. Using CRISPR/Cas9 technology, we engineered chromosome bridges with precisely defined intercentromeric distances in human RPE-1 cells. Our study revealed a decline in the frequency of chromosome bridges as cells progressed from early anaphase to late telophase, indicating resolution during mitosis. Moreover, the longer the bridging chromatin length, the higher the frequency of chromosome bridges observed at the mitotic exit, demonstrating that the size of the bridge influences its resolution during mitosis. Additionally, the separation between the bridge kinetochores needed for bridge breakage was strongly dependent on the megabase length of the bridging chromatin, with longer chromosome bridges requiring greater separation for their resolution. Given that chromosome bridge resolution occurs in a concerted manner with spindle elongation and is influenced by the length of the bridging chromatin, we posit that the traction forces generated by microtubules attaching to dicentric chromosomes play a significant role in resolving chromosome bridges during mitosis. Our study underscores the intricate interplay between chromosome bridge geometry and mechanical forces in mitotic chromosome bridge resolution. Our model offers a valuable framework for future investigations into the molecular mechanisms underlying chromosome bridge resolution, with potential implications for cancer biology and genomic stability maintenance.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/311916
https://dx.doi.org/urn:doi:10.1096/fj.202402258RR
url https://ddd.uab.cat/record/311916
https://dx.doi.org/urn:doi:10.1096/fj.202402258RR
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2021/SGR-122
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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