MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils

Autores
Campo, Vanina Andrea; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; Jiricny, Josef; di Noia, Javier M.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a 'homeologous' recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6-/- and Pms2-/- DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVk GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of 'homeologous' recombination insensitive to MMR.
Fil: Campo, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Patenaude, Anne-Marie. University of Montreal; Canadá
Fil: Kaden, Svenja. Universitat Zurich; Suiza
Fil: Horb, Lori. University of Montreal; Canadá
Fil: Firka, Daniel. University of Montreal; Canadá
Fil: Jiricny, Josef. Universitat Zurich; Suiza
Fil: di Noia, Javier M.. University of Montreal; Canadá
Materia
Antibody Gene Diversification
Mismatch Repair
Homeologous Recombination
Inmunoglobulin Gene Conversion
Activation Induced Deaminase
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:11336/84136
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/84136
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracilsCampo, Vanina AndreaPatenaude, Anne-MarieKaden, SvenjaHorb, LoriFirka, DanielJiricny, Josefdi Noia, Javier M.Antibody Gene DiversificationMismatch RepairHomeologous RecombinationInmunoglobulin Gene ConversionActivation Induced Deaminasehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a 'homeologous' recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6-/- and Pms2-/- DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVk GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of 'homeologous' recombination insensitive to MMR.Fil: Campo, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Patenaude, Anne-Marie. University of Montreal; CanadáFil: Kaden, Svenja. Universitat Zurich; SuizaFil: Horb, Lori. University of Montreal; CanadáFil: Firka, Daniel. University of Montreal; CanadáFil: Jiricny, Josef. Universitat Zurich; SuizaFil: di Noia, Javier M.. University of Montreal; CanadáOxford University Press2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/84136Campo, Vanina Andrea; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; et al.; MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils; Oxford University Press; Nucleic Acids Research; 41; 5; 3-2013; 3032-30460305-10481362-4962CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gks1470info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/article/41/5/3032/2414682info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:23:30Zoai:ri.conicet.gov.ar:11336/84136instacron: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 15:23:30.666CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
title MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
spellingShingle MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
Campo, Vanina Andrea
Antibody Gene Diversification
Mismatch Repair
Homeologous Recombination
Inmunoglobulin Gene Conversion
Activation Induced Deaminase
title_short MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
title_full MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
title_fullStr MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
title_full_unstemmed MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
title_sort MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils
dc.creator.none.fl_str_mv Campo, Vanina Andrea
Patenaude, Anne-Marie
Kaden, Svenja
Horb, Lori
Firka, Daniel
Jiricny, Josef
di Noia, Javier M.
author Campo, Vanina Andrea
author_facet Campo, Vanina Andrea
Patenaude, Anne-Marie
Kaden, Svenja
Horb, Lori
Firka, Daniel
Jiricny, Josef
di Noia, Javier M.
author_role author
author2 Patenaude, Anne-Marie
Kaden, Svenja
Horb, Lori
Firka, Daniel
Jiricny, Josef
di Noia, Javier M.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Antibody Gene Diversification
Mismatch Repair
Homeologous Recombination
Inmunoglobulin Gene Conversion
Activation Induced Deaminase
topic Antibody Gene Diversification
Mismatch Repair
Homeologous Recombination
Inmunoglobulin Gene Conversion
Activation Induced Deaminase
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a 'homeologous' recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6-/- and Pms2-/- DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVk GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of 'homeologous' recombination insensitive to MMR.
Fil: Campo, Vanina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Patenaude, Anne-Marie. University of Montreal; Canadá
Fil: Kaden, Svenja. Universitat Zurich; Suiza
Fil: Horb, Lori. University of Montreal; Canadá
Fil: Firka, Daniel. University of Montreal; Canadá
Fil: Jiricny, Josef. Universitat Zurich; Suiza
Fil: di Noia, Javier M.. University of Montreal; Canadá
description The mammalian antibody repertoire is shaped by somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) loci of B lymphocytes. SHM and CSR are triggered by non-canonical, error-prone processing of G/U mismatches generated by activation-induced deaminase (AID). In birds, AID does not trigger SHM, but it triggers Ig gene conversion (GC), a 'homeologous' recombination process involving the Ig variable region and proximal pseudogenes. Because recombination fidelity is controlled by the mismatch repair (MMR) system, we investigated whether MMR affects GC in the chicken B cell line DT40. We show here that Msh6-/- and Pms2-/- DT40 cells display cell cycle defects, including genomic re-replication. However, although IgVk GC tracts in MMR-deficient cells were slightly longer than in normal cells, Ig GC frequency, donor choice or the number of mutations per sequence remained unaltered. The finding that the avian MMR system, unlike that of mammals, does not seem to contribute towards the processing of G/U mismatches in vitro could explain why MMR is unable to initiate Ig GC in this species, despite initiating SHM and CSR in mammalian cells. Moreover, as MMR does not counteract or govern Ig GC, we report a rare example of 'homeologous' recombination insensitive to MMR.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
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/11336/84136
Campo, Vanina Andrea; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; et al.; MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils; Oxford University Press; Nucleic Acids Research; 41; 5; 3-2013; 3032-3046
0305-1048
1362-4962
CONICET Digital
CONICET
url http://hdl.handle.net/11336/84136
identifier_str_mv Campo, Vanina Andrea; Patenaude, Anne-Marie; Kaden, Svenja; Horb, Lori; Firka, Daniel; et al.; MSH6- or PMS2-deficiency causes re-replication in DT40 B cells, but it has little effect on immunoglobulin gene conversion or on repair of AID-generated uracils; Oxford University Press; Nucleic Acids Research; 41; 5; 3-2013; 3032-3046
0305-1048
1362-4962
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/nar/gks1470
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/nar/article/41/5/3032/2414682
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 Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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