Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1016/j.canlet.2011.09.019 http://repositorio.unifesp.br/handle/11600/34339 |
Resumo: | Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. in fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA. (C) 2011 Elsevier Ireland Ltd. All rights reserved. |
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Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesionsDoxorubicinDNA polymerase eta (pol eta)XPVXPALY294002DNA repairDoxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. in fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.Univ São Paulo, Dept Microbiol, Inst Biomed Sci, São Paulo, BrazilUniv Paris Sud, Inst Gustave Roussy, Ctr Natl Rech Sci, UMR8200, Villejuif, FranceFed Univ São Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilUniv Fed Rio Grande do Sul, Ctr Biotechnol, Dept Biophys, Porto Alegre, RS, BrazilFed Univ Hlth Sci Porto Alegre UFCSPA, Dept Basic Hlth Sci, Porto Alegre, RS, BrazilFed Univ São Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)USP-COFECUB (São Paulo, Brazil)Elsevier B.V.Universidade de São Paulo (USP)Univ Paris SudUniversidade Federal de São Paulo (UNIFESP)Univ Fed Rio Grande do SulFed Univ Hlth Sci Porto Alegre UFCSPAMoraes, Maria Carolina S.Andrade, Annabel Quinet deCarvalho, Helotonio [UNIFESP]Guecheva, TemenougaAgnoletto, Mateus H.Henriques, Joao A. P.Sarasin, AlainStary, AnneSaffi, JeniferMenck, Carlos F. M.2016-01-24T14:17:35Z2016-01-24T14:17:35Z2012-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion108-118application/pdfhttp://dx.doi.org/10.1016/j.canlet.2011.09.019Cancer Letters. Clare: Elsevier B.V., v. 314, n. 1, p. 108-118, 2012.10.1016/j.canlet.2011.09.019WOS000298531900012.pdf0304-3835http://repositorio.unifesp.br/handle/11600/34339WOS:000298531900012engCancer Lettersinfo:eu-repo/semantics/openAccesshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policyreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-08T10:00:15Zoai:repositorio.unifesp.br/:11600/34339Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-08T10:00:15Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions |
title |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions |
spellingShingle |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions Moraes, Maria Carolina S. Doxorubicin DNA polymerase eta (pol eta) XPV XPA LY294002 DNA repair |
title_short |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions |
title_full |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions |
title_fullStr |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions |
title_full_unstemmed |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions |
title_sort |
Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions |
author |
Moraes, Maria Carolina S. |
author_facet |
Moraes, Maria Carolina S. Andrade, Annabel Quinet de Carvalho, Helotonio [UNIFESP] Guecheva, Temenouga Agnoletto, Mateus H. Henriques, Joao A. P. Sarasin, Alain Stary, Anne Saffi, Jenifer Menck, Carlos F. M. |
author_role |
author |
author2 |
Andrade, Annabel Quinet de Carvalho, Helotonio [UNIFESP] Guecheva, Temenouga Agnoletto, Mateus H. Henriques, Joao A. P. Sarasin, Alain Stary, Anne Saffi, Jenifer Menck, Carlos F. M. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Univ Paris Sud Universidade Federal de São Paulo (UNIFESP) Univ Fed Rio Grande do Sul Fed Univ Hlth Sci Porto Alegre UFCSPA |
dc.contributor.author.fl_str_mv |
Moraes, Maria Carolina S. Andrade, Annabel Quinet de Carvalho, Helotonio [UNIFESP] Guecheva, Temenouga Agnoletto, Mateus H. Henriques, Joao A. P. Sarasin, Alain Stary, Anne Saffi, Jenifer Menck, Carlos F. M. |
dc.subject.por.fl_str_mv |
Doxorubicin DNA polymerase eta (pol eta) XPV XPA LY294002 DNA repair |
topic |
Doxorubicin DNA polymerase eta (pol eta) XPV XPA LY294002 DNA repair |
description |
Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. in fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA. (C) 2011 Elsevier Ireland Ltd. All rights reserved. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-01-01 2016-01-24T14:17:35Z 2016-01-24T14:17:35Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.canlet.2011.09.019 Cancer Letters. Clare: Elsevier B.V., v. 314, n. 1, p. 108-118, 2012. 10.1016/j.canlet.2011.09.019 WOS000298531900012.pdf 0304-3835 http://repositorio.unifesp.br/handle/11600/34339 WOS:000298531900012 |
url |
http://dx.doi.org/10.1016/j.canlet.2011.09.019 http://repositorio.unifesp.br/handle/11600/34339 |
identifier_str_mv |
Cancer Letters. Clare: Elsevier B.V., v. 314, n. 1, p. 108-118, 2012. 10.1016/j.canlet.2011.09.019 WOS000298531900012.pdf 0304-3835 WOS:000298531900012 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Cancer Letters |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy |
dc.format.none.fl_str_mv |
108-118 application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1824718335056543744 |