Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis

Homologous recombination (HR) is the principal mechanism of DNA repair acting during meiosis and is fundamental for the segregation of chromosomes and the increase of genetic diversity. Nevertheless, non-homologous end joining (NHEJ) mechanisms can also act during meiosis, mainly in response to exog...

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Autores: Enguita-Marruedo, Andrea, Martín-Ruiz, Marta, García, Eva, Gil-Fernández, Ana, Parra Catalán, María Teresa, Viera Vicario, Alberto, Rufas, Julio S., Page Utrilla, Jesús
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/687378
Acceso en línea:http://hdl.handle.net/10486/687378
https://dx.doi.org/10.1371/journal.pgen.1007439
Access Level:acceso abierto
Palabra clave:meiosis
recombination, genetic
homologous chromosome
Biología y Biomedicina / Biología
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spelling Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosisEnguita-Marruedo, AndreaMartín-Ruiz, MartaGarcía, EvaGil-Fernández, AnaParra Catalán, María TeresaViera Vicario, AlbertoRufas, Julio S.Page Utrilla, Jesúsmeiosisrecombination, genetichomologous chromosomeBiología y Biomedicina / BiologíaHomologous recombination (HR) is the principal mechanism of DNA repair acting during meiosis and is fundamental for the segregation of chromosomes and the increase of genetic diversity. Nevertheless, non-homologous end joining (NHEJ) mechanisms can also act during meiosis, mainly in response to exogenously-induced DNA damage in late stages of first meiotic prophase. In order to better understand the relationship between these two repair pathways, we studied the response to DNA damage during male mouse meiosis after gamma radiation. We clearly discerned two types of responses immediately after treatment. From leptotene to early pachytene, exogenous damage triggered the massive presence of γH2AX throughout the nucleus, which was associated with DNA repair mediated by HR components (DMC1 and RAD51). This early pathway finished with the sequential removal of DMC1 and RAD51 and was no longer inducible at mid pachytene. However, from mid-pachytene to diplotene, γH2AX appeared as large discrete foci. This late repair pattern was mediated initially by NHEJ, involving Ku70 and XRCC4, which were constitutively present, and 53BP1, which appeared at sites of damage soon after irradiation. Nevertheless, 24 hours after irradiation, a HR pathway involving RAD51 but not DMC1 mostly replaced NHEJ. Additionally, we observed the occurrence of synaptonemal complex bridges between bivalents, most likely representing chromosome translocation events that may involve DMC1, RAD51 or 53BP1. Our results reinforce the idea that the early “meiotic” repair pathway that acts by default at the beginning of meiosis is replaced from mid-pachytene onwards by a “somatic-like” repair pattern. This shift might be important to resolve DNA damage (either endogenous or exogenous) that could not be repaired by the early meiotic mechanisms, for instance those in the sex chromosomes, which lack a homologous chromosome to repair with. This transition represents another layer of functional changes that occur in meiotic cells during mid pachytene, in addition to epigenetic reprograming, reactivation of transcription, changes in the gene expression profile and acquisition of competence to proceed to metaphaseThis work was supported by grants BFU2009-10987 from the Ministerio de Ciencia e Innovacio´n and CGL2014-53106-P from the Ministerio de Economia y Competitividad (Spain)Public Library of ScienceDepartamento de BiologíaFacultad de Ciencias20192019-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/687378https://dx.doi.org/10.1371/journal.pgen.1007439reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6873782026-06-23T12:46:27Z
dc.title.none.fl_str_mv Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
title Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
spellingShingle Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
Enguita-Marruedo, Andrea
meiosis
recombination, genetic
homologous chromosome
Biología y Biomedicina / Biología
title_short Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
title_full Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
title_fullStr Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
title_full_unstemmed Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
title_sort Transition from a meiotic to a somatic-like DNA damage response during the pachytene stage in mouse meiosis
dc.creator.none.fl_str_mv Enguita-Marruedo, Andrea
Martín-Ruiz, Marta
García, Eva
Gil-Fernández, Ana
Parra Catalán, María Teresa
Viera Vicario, Alberto
Rufas, Julio S.
Page Utrilla, Jesús
author Enguita-Marruedo, Andrea
author_facet Enguita-Marruedo, Andrea
Martín-Ruiz, Marta
García, Eva
Gil-Fernández, Ana
Parra Catalán, María Teresa
Viera Vicario, Alberto
Rufas, Julio S.
Page Utrilla, Jesús
author_role author
author2 Martín-Ruiz, Marta
García, Eva
Gil-Fernández, Ana
Parra Catalán, María Teresa
Viera Vicario, Alberto
Rufas, Julio S.
Page Utrilla, Jesús
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología
Facultad de Ciencias
dc.subject.none.fl_str_mv meiosis
recombination, genetic
homologous chromosome
Biología y Biomedicina / Biología
topic meiosis
recombination, genetic
homologous chromosome
Biología y Biomedicina / Biología
description Homologous recombination (HR) is the principal mechanism of DNA repair acting during meiosis and is fundamental for the segregation of chromosomes and the increase of genetic diversity. Nevertheless, non-homologous end joining (NHEJ) mechanisms can also act during meiosis, mainly in response to exogenously-induced DNA damage in late stages of first meiotic prophase. In order to better understand the relationship between these two repair pathways, we studied the response to DNA damage during male mouse meiosis after gamma radiation. We clearly discerned two types of responses immediately after treatment. From leptotene to early pachytene, exogenous damage triggered the massive presence of γH2AX throughout the nucleus, which was associated with DNA repair mediated by HR components (DMC1 and RAD51). This early pathway finished with the sequential removal of DMC1 and RAD51 and was no longer inducible at mid pachytene. However, from mid-pachytene to diplotene, γH2AX appeared as large discrete foci. This late repair pattern was mediated initially by NHEJ, involving Ku70 and XRCC4, which were constitutively present, and 53BP1, which appeared at sites of damage soon after irradiation. Nevertheless, 24 hours after irradiation, a HR pathway involving RAD51 but not DMC1 mostly replaced NHEJ. Additionally, we observed the occurrence of synaptonemal complex bridges between bivalents, most likely representing chromosome translocation events that may involve DMC1, RAD51 or 53BP1. Our results reinforce the idea that the early “meiotic” repair pathway that acts by default at the beginning of meiosis is replaced from mid-pachytene onwards by a “somatic-like” repair pattern. This shift might be important to resolve DNA damage (either endogenous or exogenous) that could not be repaired by the early meiotic mechanisms, for instance those in the sex chromosomes, which lack a homologous chromosome to repair with. This transition represents another layer of functional changes that occur in meiotic cells during mid pachytene, in addition to epigenetic reprograming, reactivation of transcription, changes in the gene expression profile and acquisition of competence to proceed to metaphase
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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 http://hdl.handle.net/10486/687378
https://dx.doi.org/10.1371/journal.pgen.1007439
url http://hdl.handle.net/10486/687378
https://dx.doi.org/10.1371/journal.pgen.1007439
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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