A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1

[EN]Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with three cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the H...

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Autores: Felipe-Medina, Natalia, Caburet, Sandrine, Sánchez Sáez, Fernando, Condezo, Yazmine B, de Rooij, Dirk G, Gómez-H, Laura, Garcia-Valiente, Rodrigo, Todeschini, Anne Laure, Duque, Paloma, Sánchez Martín, Manuel Adolfo, Shalev, Stavit A, Llano Cuadra, María Elena, Veitia, Reiner A, Martín Pendás, Alberto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/168742
Acceso en línea:http://hdl.handle.net/10366/168742
Access Level:acceso abierto
Palabra clave:meiosis POI
Meiosis
Mutation
Primary Ovarian Insufficiency
Animals
Rad51 Recombinase
DNA-Binding Proteins
Mice
meiosis
insuficiencia ovárica primaria
animales
ratones
mutación
proteínas de unión al ADN
rad51 recombinasa
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oai_identifier_str oai:gredos.usal.es:10366/168742
network_acronym_str ES
network_name_str España
repository_id_str
spelling A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1Felipe-Medina, NataliaCaburet, SandrineSánchez Sáez, FernandoCondezo, Yazmine Bde Rooij, Dirk GGómez-H, LauraGarcia-Valiente, RodrigoTodeschini, Anne LaureDuque, PalomaSánchez Martín, Manuel AdolfoShalev, Stavit ALlano Cuadra, María ElenaVeitia, Reiner AMartín Pendás, Albertomeiosis POIMeiosisMutationPrimary Ovarian InsufficiencyAnimalsRad51 RecombinaseDNA-Binding ProteinsMicemeiosisinsuficiencia ovárica primariaanimalesratonesmutaciónproteínas de unión al ADNrad51 recombinasa[EN]Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with three cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse showed that it behaves as a hypomorphic allele compared to a new loss-of-function (knock-out) mouse model. Hsf2bpS167L/S167L females show reduced fertility with smaller litter sizes. To obtain mechanistic insights, we identified C19ORF57/BRME1 as a strong interactor and stabilizer of HSF2BP and showed that the BRME1/HSF2BP protein complex co-immunoprecipitates with BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L variant showed a strongly decreased staining of both HSF2BP and BRME1 at the recombination nodules and a reduced number of the foci formed by the recombinases RAD51/DMC1, thus leading to a lower frequency of crossovers. Our results provide insights into the molecular mechanism of HSF2BP-S167L in human ovarian insufficiency and sub(in)fertility.202620262020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10366/168742reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésMinisterio de Economia y Competitividad (BFU2017-89408-R)Attribution-NonCommercial-NoDerivatives 4.0 InternacionalAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1687422026-06-07T06:28:51Z
dc.title.none.fl_str_mv A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
title A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
spellingShingle A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
Felipe-Medina, Natalia
meiosis POI
Meiosis
Mutation
Primary Ovarian Insufficiency
Animals
Rad51 Recombinase
DNA-Binding Proteins
Mice
meiosis
insuficiencia ovárica primaria
animales
ratones
mutación
proteínas de unión al ADN
rad51 recombinasa
title_short A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
title_full A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
title_fullStr A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
title_full_unstemmed A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
title_sort A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1
dc.creator.none.fl_str_mv Felipe-Medina, Natalia
Caburet, Sandrine
Sánchez Sáez, Fernando
Condezo, Yazmine B
de Rooij, Dirk G
Gómez-H, Laura
Garcia-Valiente, Rodrigo
Todeschini, Anne Laure
Duque, Paloma
Sánchez Martín, Manuel Adolfo
Shalev, Stavit A
Llano Cuadra, María Elena
Veitia, Reiner A
Martín Pendás, Alberto
author Felipe-Medina, Natalia
author_facet Felipe-Medina, Natalia
Caburet, Sandrine
Sánchez Sáez, Fernando
Condezo, Yazmine B
de Rooij, Dirk G
Gómez-H, Laura
Garcia-Valiente, Rodrigo
Todeschini, Anne Laure
Duque, Paloma
Sánchez Martín, Manuel Adolfo
Shalev, Stavit A
Llano Cuadra, María Elena
Veitia, Reiner A
Martín Pendás, Alberto
author_role author
author2 Caburet, Sandrine
Sánchez Sáez, Fernando
Condezo, Yazmine B
de Rooij, Dirk G
Gómez-H, Laura
Garcia-Valiente, Rodrigo
Todeschini, Anne Laure
Duque, Paloma
Sánchez Martín, Manuel Adolfo
Shalev, Stavit A
Llano Cuadra, María Elena
Veitia, Reiner A
Martín Pendás, Alberto
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv meiosis POI
Meiosis
Mutation
Primary Ovarian Insufficiency
Animals
Rad51 Recombinase
DNA-Binding Proteins
Mice
meiosis
insuficiencia ovárica primaria
animales
ratones
mutación
proteínas de unión al ADN
rad51 recombinasa
topic meiosis POI
Meiosis
Mutation
Primary Ovarian Insufficiency
Animals
Rad51 Recombinase
DNA-Binding Proteins
Mice
meiosis
insuficiencia ovárica primaria
animales
ratones
mutación
proteínas de unión al ADN
rad51 recombinasa
description [EN]Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with three cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse showed that it behaves as a hypomorphic allele compared to a new loss-of-function (knock-out) mouse model. Hsf2bpS167L/S167L females show reduced fertility with smaller litter sizes. To obtain mechanistic insights, we identified C19ORF57/BRME1 as a strong interactor and stabilizer of HSF2BP and showed that the BRME1/HSF2BP protein complex co-immunoprecipitates with BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L variant showed a strongly decreased staining of both HSF2BP and BRME1 at the recombination nodules and a reduced number of the foci formed by the recombinases RAD51/DMC1, thus leading to a lower frequency of crossovers. Our results provide insights into the molecular mechanism of HSF2BP-S167L in human ovarian insufficiency and sub(in)fertility.
publishDate 2020
dc.date.none.fl_str_mv 2020
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/168742
url http://hdl.handle.net/10366/168742
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Ministerio de Economia y Competitividad (BFU2017-89408-R)
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional

Attribution-NonCommercial-NoDerivatives 4.0 Internacional

http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional

http://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:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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