DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells
- Autores
- Elguero, María Eugenia; de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The role of DNA double strand break (DSB) repair pathways, non-homologous end joining (NHEJ), and homologous recombination (HR) was evaluated to prevent the chromosome instability induced by the topoisomerase II (Top2) poisons, idarubicin, and etoposide in Chinese hamster cell lines. XR-C1 (DNA-PKcs deficient) and V-C8 (BRCA2 deficient) showed higher sensitivity to increased concentrations of Top2 poisons compared with their normal counterparts, CHO9 and V79. Both proficient and deficient cells exhibited a marked DSB induction in all phases of the cell cycle. Additionally, deficient cells showed persistent DNA damage 24 hr post-treatment. Chromosomal aberrations increased in the first mitosis following Top2 poison-treatments in G1 or G2 in proficient and deficient cells. CHO9 and V79 demonstrated chromosome and chromatid exchanges following treatments in G1 and G2 phases, respectively. Deficient cells showed high frequencies of chromatid exchanges following treatments in G1 and G2. Simultaneously, we analyzed the micronuclei (MN) induction in interphase cells after treatments in G1, S, or G2 of the previous cell cycle. Both Top2 poisons induced an important increase in MN in CHO9, V79, and V-C8 cells. XR-C1 exhibited an increased MN frequency when cells were treated in G1 phase but not in S or G2. This MN reduction was due to a cell accumulation at G2/M and death in G2-treated cells. Our data suggest that NHEJ and HR operate differentially throughout the cell cycle to protect from Top2 poison-induced chromosome instability, and that DNA-PKcs-dependent NHEJ pathway allows the survival of chromosome damaged cells during S/G2 to the next interphase. © 2012 Wiley Periodicals, Inc.
Fil: Elguero, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Gonzalez Cid, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina - Materia
-
Chinese Hamster Cell Lines
Chromosome Integrity
Double Strand Break Repair
Etoposide
Idarubicin
Micronucleus - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/52790
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DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cellsElguero, María Eugeniade Campos Nebel, Ildefonso MarceloGonzalez Cid, Marcela BeatrizChinese Hamster Cell LinesChromosome IntegrityDouble Strand Break RepairEtoposideIdarubicinMicronucleushttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The role of DNA double strand break (DSB) repair pathways, non-homologous end joining (NHEJ), and homologous recombination (HR) was evaluated to prevent the chromosome instability induced by the topoisomerase II (Top2) poisons, idarubicin, and etoposide in Chinese hamster cell lines. XR-C1 (DNA-PKcs deficient) and V-C8 (BRCA2 deficient) showed higher sensitivity to increased concentrations of Top2 poisons compared with their normal counterparts, CHO9 and V79. Both proficient and deficient cells exhibited a marked DSB induction in all phases of the cell cycle. Additionally, deficient cells showed persistent DNA damage 24 hr post-treatment. Chromosomal aberrations increased in the first mitosis following Top2 poison-treatments in G1 or G2 in proficient and deficient cells. CHO9 and V79 demonstrated chromosome and chromatid exchanges following treatments in G1 and G2 phases, respectively. Deficient cells showed high frequencies of chromatid exchanges following treatments in G1 and G2. Simultaneously, we analyzed the micronuclei (MN) induction in interphase cells after treatments in G1, S, or G2 of the previous cell cycle. Both Top2 poisons induced an important increase in MN in CHO9, V79, and V-C8 cells. XR-C1 exhibited an increased MN frequency when cells were treated in G1 phase but not in S or G2. This MN reduction was due to a cell accumulation at G2/M and death in G2-treated cells. Our data suggest that NHEJ and HR operate differentially throughout the cell cycle to protect from Top2 poison-induced chromosome instability, and that DNA-PKcs-dependent NHEJ pathway allows the survival of chromosome damaged cells during S/G2 to the next interphase. © 2012 Wiley Periodicals, Inc.Fil: Elguero, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gonzalez Cid, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaWiley-liss, Div John Wiley & Sons Inc2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52790Elguero, María Eugenia; de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz; DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells; Wiley-liss, Div John Wiley & Sons Inc; Environmental And Molecular Mutagenesis; 53; 8; 10-2012; 608-6180893-6692CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/em.21729info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/em.21729info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:12:58Zoai:ri.conicet.gov.ar:11336/52790instacron: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:34982025-09-29 10:12:58.916CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells |
title |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells |
spellingShingle |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells Elguero, María Eugenia Chinese Hamster Cell Lines Chromosome Integrity Double Strand Break Repair Etoposide Idarubicin Micronucleus |
title_short |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells |
title_full |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells |
title_fullStr |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells |
title_full_unstemmed |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells |
title_sort |
DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells |
dc.creator.none.fl_str_mv |
Elguero, María Eugenia de Campos Nebel, Ildefonso Marcelo Gonzalez Cid, Marcela Beatriz |
author |
Elguero, María Eugenia |
author_facet |
Elguero, María Eugenia de Campos Nebel, Ildefonso Marcelo Gonzalez Cid, Marcela Beatriz |
author_role |
author |
author2 |
de Campos Nebel, Ildefonso Marcelo Gonzalez Cid, Marcela Beatriz |
author2_role |
author author |
dc.subject.none.fl_str_mv |
Chinese Hamster Cell Lines Chromosome Integrity Double Strand Break Repair Etoposide Idarubicin Micronucleus |
topic |
Chinese Hamster Cell Lines Chromosome Integrity Double Strand Break Repair Etoposide Idarubicin Micronucleus |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
The role of DNA double strand break (DSB) repair pathways, non-homologous end joining (NHEJ), and homologous recombination (HR) was evaluated to prevent the chromosome instability induced by the topoisomerase II (Top2) poisons, idarubicin, and etoposide in Chinese hamster cell lines. XR-C1 (DNA-PKcs deficient) and V-C8 (BRCA2 deficient) showed higher sensitivity to increased concentrations of Top2 poisons compared with their normal counterparts, CHO9 and V79. Both proficient and deficient cells exhibited a marked DSB induction in all phases of the cell cycle. Additionally, deficient cells showed persistent DNA damage 24 hr post-treatment. Chromosomal aberrations increased in the first mitosis following Top2 poison-treatments in G1 or G2 in proficient and deficient cells. CHO9 and V79 demonstrated chromosome and chromatid exchanges following treatments in G1 and G2 phases, respectively. Deficient cells showed high frequencies of chromatid exchanges following treatments in G1 and G2. Simultaneously, we analyzed the micronuclei (MN) induction in interphase cells after treatments in G1, S, or G2 of the previous cell cycle. Both Top2 poisons induced an important increase in MN in CHO9, V79, and V-C8 cells. XR-C1 exhibited an increased MN frequency when cells were treated in G1 phase but not in S or G2. This MN reduction was due to a cell accumulation at G2/M and death in G2-treated cells. Our data suggest that NHEJ and HR operate differentially throughout the cell cycle to protect from Top2 poison-induced chromosome instability, and that DNA-PKcs-dependent NHEJ pathway allows the survival of chromosome damaged cells during S/G2 to the next interphase. © 2012 Wiley Periodicals, Inc. Fil: Elguero, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: de Campos Nebel, Ildefonso Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Gonzalez Cid, Marcela Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina |
description |
The role of DNA double strand break (DSB) repair pathways, non-homologous end joining (NHEJ), and homologous recombination (HR) was evaluated to prevent the chromosome instability induced by the topoisomerase II (Top2) poisons, idarubicin, and etoposide in Chinese hamster cell lines. XR-C1 (DNA-PKcs deficient) and V-C8 (BRCA2 deficient) showed higher sensitivity to increased concentrations of Top2 poisons compared with their normal counterparts, CHO9 and V79. Both proficient and deficient cells exhibited a marked DSB induction in all phases of the cell cycle. Additionally, deficient cells showed persistent DNA damage 24 hr post-treatment. Chromosomal aberrations increased in the first mitosis following Top2 poison-treatments in G1 or G2 in proficient and deficient cells. CHO9 and V79 demonstrated chromosome and chromatid exchanges following treatments in G1 and G2 phases, respectively. Deficient cells showed high frequencies of chromatid exchanges following treatments in G1 and G2. Simultaneously, we analyzed the micronuclei (MN) induction in interphase cells after treatments in G1, S, or G2 of the previous cell cycle. Both Top2 poisons induced an important increase in MN in CHO9, V79, and V-C8 cells. XR-C1 exhibited an increased MN frequency when cells were treated in G1 phase but not in S or G2. This MN reduction was due to a cell accumulation at G2/M and death in G2-treated cells. Our data suggest that NHEJ and HR operate differentially throughout the cell cycle to protect from Top2 poison-induced chromosome instability, and that DNA-PKcs-dependent NHEJ pathway allows the survival of chromosome damaged cells during S/G2 to the next interphase. © 2012 Wiley Periodicals, Inc. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-10 |
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/11336/52790 Elguero, María Eugenia; de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz; DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells; Wiley-liss, Div John Wiley & Sons Inc; Environmental And Molecular Mutagenesis; 53; 8; 10-2012; 608-618 0893-6692 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/52790 |
identifier_str_mv |
Elguero, María Eugenia; de Campos Nebel, Ildefonso Marcelo; Gonzalez Cid, Marcela Beatriz; DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells; Wiley-liss, Div John Wiley & Sons Inc; Environmental And Molecular Mutagenesis; 53; 8; 10-2012; 608-618 0893-6692 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1002/em.21729 info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/em.21729 |
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 application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Wiley-liss, Div John Wiley & Sons Inc |
publisher.none.fl_str_mv |
Wiley-liss, Div John Wiley & Sons Inc |
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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13.070432 |