Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging

Autores
Martin Guerrero, Idoia; de Prado, Elena; López López, Elixabet; Ardanaz, Maite; Vitoria, Juan Carlos; Parada, Luis Antonio; García Orad, Cristina; García Orad, Africa
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover, fidelity of this pathway has been shown to decline with age. Although the mechanism underlying this inefficacy is unknown, other repair pathways are inactivated by methylation with aging. In this study, we analyzed the implication of NHEJ genes methylation in the increase of translocations with the age. To this aim, we determined the relationship between translocations and aging in 565 Spanish healthy individuals and correlated these data with the methylation status of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major) translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and XRCC6) presented age-dependent promoter methylation changes. However, we did not observe a correlation between the increase of translocations and methylation, indicating that other molecular mechanisms are involved in the loss of NHEJ fidelity with aging.
Fil: Martin Guerrero, Idoia. Universidad del Pais Vasco; España
Fil: de Prado, Elena. Universidad del Pais Vasco; España
Fil: López López, Elixabet. Universidad del Pais Vasco; España
Fil: Ardanaz, Maite. Hospital Txagorritxu; España
Fil: Vitoria, Juan Carlos. Hospital de Cruces; España
Fil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
Fil: García Orad, Cristina. Hospital General Valencia; España
Fil: García Orad, Africa. BioCruces Health Research Institute; España. Universidad del Pais Vasco; España
Materia
Dna Methylation
Chromosome Translocation
Age
Nhej
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7233
Acceder
id CONICETDig_442f8c35f930d07f9027eda824649ed7
oai_identifier_str oai:ri.conicet.gov.ar:11336/7233
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with agingMartin Guerrero, Idoiade Prado, ElenaLópez López, ElixabetArdanaz, MaiteVitoria, Juan CarlosParada, Luis AntonioGarcía Orad, CristinaGarcía Orad, AfricaDna MethylationChromosome TranslocationAgeNhejhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover, fidelity of this pathway has been shown to decline with age. Although the mechanism underlying this inefficacy is unknown, other repair pathways are inactivated by methylation with aging. In this study, we analyzed the implication of NHEJ genes methylation in the increase of translocations with the age. To this aim, we determined the relationship between translocations and aging in 565 Spanish healthy individuals and correlated these data with the methylation status of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major) translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and XRCC6) presented age-dependent promoter methylation changes. However, we did not observe a correlation between the increase of translocations and methylation, indicating that other molecular mechanisms are involved in the loss of NHEJ fidelity with aging.Fil: Martin Guerrero, Idoia. Universidad del Pais Vasco; EspañaFil: de Prado, Elena. Universidad del Pais Vasco; EspañaFil: López López, Elixabet. Universidad del Pais Vasco; EspañaFil: Ardanaz, Maite. Hospital Txagorritxu; EspañaFil: Vitoria, Juan Carlos. Hospital de Cruces; EspañaFil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; ArgentinaFil: García Orad, Cristina. Hospital General Valencia; EspañaFil: García Orad, Africa. BioCruces Health Research Institute; España. Universidad del Pais Vasco; EspañaSpringer2014-11-16info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7233Martin Guerrero, Idoia; de Prado, Elena; López López, Elixabet; Ardanaz, Maite; Vitoria, Juan Carlos; et al.; Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging; Springer; Age; 36; 6; 16-11-20140161-9152enginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s11357-014-9730-4info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs11357-014-9730-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:21:50Zoai:ri.conicet.gov.ar:11336/7233instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:21:51.174CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
title Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
spellingShingle Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
Martin Guerrero, Idoia
Dna Methylation
Chromosome Translocation
Age
Nhej
title_short Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
title_full Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
title_fullStr Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
title_full_unstemmed Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
title_sort Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging
dc.creator.none.fl_str_mv Martin Guerrero, Idoia
de Prado, Elena
López López, Elixabet
Ardanaz, Maite
Vitoria, Juan Carlos
Parada, Luis Antonio
García Orad, Cristina
García Orad, Africa
author Martin Guerrero, Idoia
author_facet Martin Guerrero, Idoia
de Prado, Elena
López López, Elixabet
Ardanaz, Maite
Vitoria, Juan Carlos
Parada, Luis Antonio
García Orad, Cristina
García Orad, Africa
author_role author
author2 de Prado, Elena
López López, Elixabet
Ardanaz, Maite
Vitoria, Juan Carlos
Parada, Luis Antonio
García Orad, Cristina
García Orad, Africa
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dna Methylation
Chromosome Translocation
Age
Nhej
topic Dna Methylation
Chromosome Translocation
Age
Nhej
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover, fidelity of this pathway has been shown to decline with age. Although the mechanism underlying this inefficacy is unknown, other repair pathways are inactivated by methylation with aging. In this study, we analyzed the implication of NHEJ genes methylation in the increase of translocations with the age. To this aim, we determined the relationship between translocations and aging in 565 Spanish healthy individuals and correlated these data with the methylation status of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major) translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and XRCC6) presented age-dependent promoter methylation changes. However, we did not observe a correlation between the increase of translocations and methylation, indicating that other molecular mechanisms are involved in the loss of NHEJ fidelity with aging.
Fil: Martin Guerrero, Idoia. Universidad del Pais Vasco; España
Fil: de Prado, Elena. Universidad del Pais Vasco; España
Fil: López López, Elixabet. Universidad del Pais Vasco; España
Fil: Ardanaz, Maite. Hospital Txagorritxu; España
Fil: Vitoria, Juan Carlos. Hospital de Cruces; España
Fil: Parada, Luis Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; Argentina. Universidad Nacional de Salta; Argentina
Fil: García Orad, Cristina. Hospital General Valencia; España
Fil: García Orad, Africa. BioCruces Health Research Institute; España. Universidad del Pais Vasco; España
description Chromosome translocations are especially frequent in human lymphomas and leukemias but are insufficient to drive carcinogenesis. Indeed, several of the so-called tumor specific translocations have been detected in peripheral blood of healthy individuals, finding a higher frequency of some of them with aging. The inappropriate repair of DNA double strand breaks by the nonhomologous end joining (NHEJ) pathway is one of the reasons for a translocation to occur. Moreover, fidelity of this pathway has been shown to decline with age. Although the mechanism underlying this inefficacy is unknown, other repair pathways are inactivated by methylation with aging. In this study, we analyzed the implication of NHEJ genes methylation in the increase of translocations with the age. To this aim, we determined the relationship between translocations and aging in 565 Spanish healthy individuals and correlated these data with the methylation status of 11 NHEJ genes. We found higher frequency of BCL2-JH and BCR-ABL (major) translocations with aging. In addition, we detected that two NHEJ genes (LIG4 and XRCC6) presented age-dependent promoter methylation changes. However, we did not observe a correlation between the increase of translocations and methylation, indicating that other molecular mechanisms are involved in the loss of NHEJ fidelity with aging.
publishDate 2014
dc.date.none.fl_str_mv 2014-11-16
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/7233
Martin Guerrero, Idoia; de Prado, Elena; López López, Elixabet; Ardanaz, Maite; Vitoria, Juan Carlos; et al.; Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging; Springer; Age; 36; 6; 16-11-2014
0161-9152
url http://hdl.handle.net/11336/7233
identifier_str_mv Martin Guerrero, Idoia; de Prado, Elena; López López, Elixabet; Ardanaz, Maite; Vitoria, Juan Carlos; et al.; Methylation of the nonhomologous end joining repair pathway genes does not explain the increase of translocations with aging; Springer; Age; 36; 6; 16-11-2014
0161-9152
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s11357-014-9730-4
info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs11357-014-9730-4
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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