The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.

Autores
Gottifredi, Vanesa; Wiesmuller L
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.Gottifredi V1, Wiesmüller L2.The tumor suppressor p53 is a transcriptional factor broadly mutated in cancer. Most inactivating and gain of function mutations disrupt the sequence-specific DNA binding domain, which activates target genes. This is perhaps the main reason why most research has focused on the relevance of such transcriptional activity for the prevention or elimination of cancer cells. Notwithstanding, transcriptional regulation may not be the only mechanism underlying its role in tumor suppression and therapeutic responses. In the past, a direct role of p53 in DNA repair transactions that include the regulation of homologous recombination has been suggested. More recently, the localization of p53 at replication forks has been demonstrated and the effect of p53 on nascent DNA elongation has been explored. While some data sets indicate that the regulation of ongoing replication forks by p53 may be mediated by p53 targets such as MDM2 (murine double minute 2) and polymerase (POL) eta other evidences demonstrate that p53 is capable of controlling DNA replication by directly interacting with the replisome and altering its composition. In addition to discussing such findings, this review will also analyze the impact that p53-mediated control of ongoing DNA replication has on treatment responses and tumor suppressor abilities of this important anti-oncogene.
Fil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Wiesmuller L. Universitat Ulm; Alemania
Materia
MRE11; POL iota; POL teta; RAD52;
ZRANB3; fork reversal; mutant p53;
template switching; translesion DNA synthesis
therapy resistance
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:11336/88200

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spelling The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.Gottifredi, VanesaWiesmuller LMRE11; POL iota; POL teta; RAD52;ZRANB3; fork reversal; mutant p53;template switching; translesion DNA synthesistherapy resistancehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.Gottifredi V1, Wiesmüller L2.The tumor suppressor p53 is a transcriptional factor broadly mutated in cancer. Most inactivating and gain of function mutations disrupt the sequence-specific DNA binding domain, which activates target genes. This is perhaps the main reason why most research has focused on the relevance of such transcriptional activity for the prevention or elimination of cancer cells. Notwithstanding, transcriptional regulation may not be the only mechanism underlying its role in tumor suppression and therapeutic responses. In the past, a direct role of p53 in DNA repair transactions that include the regulation of homologous recombination has been suggested. More recently, the localization of p53 at replication forks has been demonstrated and the effect of p53 on nascent DNA elongation has been explored. While some data sets indicate that the regulation of ongoing replication forks by p53 may be mediated by p53 targets such as MDM2 (murine double minute 2) and polymerase (POL) eta other evidences demonstrate that p53 is capable of controlling DNA replication by directly interacting with the replisome and altering its composition. In addition to discussing such findings, this review will also analyze the impact that p53-mediated control of ongoing DNA replication has on treatment responses and tumor suppressor abilities of this important anti-oncogene.Fil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Wiesmuller L. Universitat Ulm; AlemaniaMDPI2018-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/88200Gottifredi, Vanesa; Wiesmuller L; The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.; MDPI; Cancers; 10; 7-2018; 1-152072-6694CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/cancers10080250info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/10/8/250info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:50Zoai:ri.conicet.gov.ar:11336/88200instacron: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 10:03:50.487CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
title The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
spellingShingle The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
Gottifredi, Vanesa
MRE11; POL iota; POL teta; RAD52;
ZRANB3; fork reversal; mutant p53;
template switching; translesion DNA synthesis
therapy resistance
title_short The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
title_full The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
title_fullStr The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
title_full_unstemmed The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
title_sort The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.
dc.creator.none.fl_str_mv Gottifredi, Vanesa
Wiesmuller L
author Gottifredi, Vanesa
author_facet Gottifredi, Vanesa
Wiesmuller L
author_role author
author2 Wiesmuller L
author2_role author
dc.subject.none.fl_str_mv MRE11; POL iota; POL teta; RAD52;
ZRANB3; fork reversal; mutant p53;
template switching; translesion DNA synthesis
therapy resistance
topic MRE11; POL iota; POL teta; RAD52;
ZRANB3; fork reversal; mutant p53;
template switching; translesion DNA synthesis
therapy resistance
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 Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.Gottifredi V1, Wiesmüller L2.The tumor suppressor p53 is a transcriptional factor broadly mutated in cancer. Most inactivating and gain of function mutations disrupt the sequence-specific DNA binding domain, which activates target genes. This is perhaps the main reason why most research has focused on the relevance of such transcriptional activity for the prevention or elimination of cancer cells. Notwithstanding, transcriptional regulation may not be the only mechanism underlying its role in tumor suppression and therapeutic responses. In the past, a direct role of p53 in DNA repair transactions that include the regulation of homologous recombination has been suggested. More recently, the localization of p53 at replication forks has been demonstrated and the effect of p53 on nascent DNA elongation has been explored. While some data sets indicate that the regulation of ongoing replication forks by p53 may be mediated by p53 targets such as MDM2 (murine double minute 2) and polymerase (POL) eta other evidences demonstrate that p53 is capable of controlling DNA replication by directly interacting with the replisome and altering its composition. In addition to discussing such findings, this review will also analyze the impact that p53-mediated control of ongoing DNA replication has on treatment responses and tumor suppressor abilities of this important anti-oncogene.
Fil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Wiesmuller L. Universitat Ulm; Alemania
description The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.Gottifredi V1, Wiesmüller L2.The tumor suppressor p53 is a transcriptional factor broadly mutated in cancer. Most inactivating and gain of function mutations disrupt the sequence-specific DNA binding domain, which activates target genes. This is perhaps the main reason why most research has focused on the relevance of such transcriptional activity for the prevention or elimination of cancer cells. Notwithstanding, transcriptional regulation may not be the only mechanism underlying its role in tumor suppression and therapeutic responses. In the past, a direct role of p53 in DNA repair transactions that include the regulation of homologous recombination has been suggested. More recently, the localization of p53 at replication forks has been demonstrated and the effect of p53 on nascent DNA elongation has been explored. While some data sets indicate that the regulation of ongoing replication forks by p53 may be mediated by p53 targets such as MDM2 (murine double minute 2) and polymerase (POL) eta other evidences demonstrate that p53 is capable of controlling DNA replication by directly interacting with the replisome and altering its composition. In addition to discussing such findings, this review will also analyze the impact that p53-mediated control of ongoing DNA replication has on treatment responses and tumor suppressor abilities of this important anti-oncogene.
publishDate 2018
dc.date.none.fl_str_mv 2018-07
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/11336/88200
Gottifredi, Vanesa; Wiesmuller L; The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.; MDPI; Cancers; 10; 7-2018; 1-15
2072-6694
CONICET Digital
CONICET
url http://hdl.handle.net/11336/88200
identifier_str_mv Gottifredi, Vanesa; Wiesmuller L; The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53.; MDPI; Cancers; 10; 7-2018; 1-15
2072-6694
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers10080250
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/10/8/250
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 MDPI
publisher.none.fl_str_mv MDPI
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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