Mostrar el registro sencillo del ítem
dc.contributor.author
Perini, Valentina
dc.contributor.author
Schacke, Michelle
dc.contributor.author
Liddle, Pablo
dc.contributor.author
Vilchez Larrea, Salomé Catalina
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Keszenman, Deborah J.
dc.contributor.author
Lafon Hughes, Laura
dc.date.available
2021-03-10T15:15:50Z
dc.date.issued
2020-11-05
dc.identifier.citation
Perini, Valentina; Schacke, Michelle; Liddle, Pablo; Vilchez Larrea, Salomé Catalina; Keszenman, Deborah J.; et al.; PARP Inhibitor Olaparib Causes No Potentiation of the Bleomycin Effect in VERO Cells, Even in the Presence of Pooled ATM, DNA-PK, and LigIV Inhibitors; MDPI AG; International Journal of Molecular Sciences; 21; 21; 5-11-2020; 1-22
dc.identifier.issn
1422-0067
dc.identifier.uri
http://hdl.handle.net/11336/127964
dc.description.abstract
Poly(ADP-ribosyl)polymerase (PARP) synthesizes poly(ADP-ribose) (PAR), which is anchored to proteins. PAR facilitates multiprotein complexes’ assembly. Nuclear PAR affects chromatin’s structure and functions, including transcriptional regulation. In response to stress, particularly genotoxic stress, PARP activation facilitates DNA damage repair. The PARP inhibitor Olaparib (OLA) displays synthetic lethality with mutated homologous recombination proteins (BRCA-1/2), base excision repair proteins (XRCC1, Polβ), and canonical nonhomologous end joining (LigIV). However, the limits of synthetic lethality are not clear. On one hand, it is unknown whether any limiting factor of homologous recombination can be a synthetic PARP lethality partner. On the other hand, some BRCA-mutated patients are not responsive to OLA for still unknown reasons. In an effort to help delineate the boundaries of synthetic lethality, we have induced DNA damage in VERO cells with the radiomimetic chemotherapeutic agent bleomycin (BLEO). A VERO subpopulation was resistant to BLEO, BLEO + OLA, and BLEO + OLA + ATM inhibitor KU55933 + DNA-PK inhibitor KU-0060648 + LigIV inhibitor SCR7 pyrazine. Regarding the mechanism(s) behind the resistance and lack of synthetic lethality, some hypotheses have been discarded and alternative hypotheses are suggested.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
MDPI AG
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CDKN2A
dc.subject
KU-0060648
dc.subject
KU55933
dc.subject
OLAPARIB
dc.subject
PARP-1
dc.subject
SCR7 PYRAZINE
dc.subject
VERO CELLS
dc.subject
POLY(ADP-RIBOSYLATION)
dc.subject
RESISTANCE
dc.subject
SYNERGISM
dc.subject.classification
Biología Celular, Microbiología
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
PARP Inhibitor Olaparib Causes No Potentiation of the Bleomycin Effect in VERO Cells, Even in the Presence of Pooled ATM, DNA-PK, and LigIV Inhibitors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-12-22T15:42:06Z
dc.journal.volume
21
dc.journal.number
21
dc.journal.pagination
1-22
dc.journal.pais
Suiza
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.description.fil
Fil: Perini, Valentina. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Schacke, Michelle. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Liddle, Pablo. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Keszenman, Deborah J.. Universidad de la Republica. Centro Universitario del Litoral Norte.; Uruguay
dc.description.fil
Fil: Lafon Hughes, Laura. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.journal.title
International Journal of Molecular Sciences
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/21/21/8288
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3390/ijms21218288
Archivos asociados