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dc.contributor.author
Alonso, Guillermo Daniel
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dc.contributor.author
Vilchez Larrea, Salomé Catalina
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dc.contributor.author
Fernandez Villamil, Silvia Hebe
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dc.contributor.other
De Bruyn, Olivier
dc.contributor.other
Peeters, Stephane
dc.date.available
2020-06-18T16:30:41Z
dc.date.issued
2010
dc.identifier.citation
Alonso, Guillermo Daniel; Vilchez Larrea, Salomé Catalina; Fernandez Villamil, Silvia Hebe; Metabolism of Poly-ADP-ribose in Trypanosomatids; Nova Science Publishers, Inc; 2010; 119-141
dc.identifier.isbn
978-1-61668-716-8
dc.identifier.uri
http://hdl.handle.net/11336/107619
dc.description.abstract
The poly-ADP-ribosylation reaction is a post-translational modification involved invarious cellular processes including DNA repair, DNA replication, gene expression,maintenance of genomic stability, cell death and cellular differentiation. Poly(ADPribose)polymerase (PARP) is an abundant nuclear protein that is potently activated by DNA strand nicks and breaks. This enzyme transfers ADP-ribose units from NAD+ to several proteins implicated in chromatin architecture and DNA metabolism, but the main acceptor protein is PARP itself. The homopolymer of ADP-ribose is mainly catabolized by poly(ADP-ribose)glycohydrolase (PARG), a mechanism through which PARP and other modified proteins may be restored to their native state. Poly-ADP-ribose metabolism has been studied in several organisms, but limited information is available about this process in trypanosomatids. In our laboratory, we have demonstrated the presence of PARP in the trypanosomatids Crithidia fasciculata, Trypanosoma cruzi and Trypanosoma brucei, all of which showed properties characterizing other representatives of the PARP group. By using the genome project of T. cruzi and T. brucei we identified TcPARP and TbPARP as well as TcPARG and TbPARG sequences and found that they presented several conserved structural characteristics and only showed slight differences when compared with PARPs and PARGs from other organisms. In addition, we characterized the purified C. fasciculata PARP and recombinant TcPARP biochemically and found that both enzymes were strongly activated by nicked DNA. We also found that histones increase PARP activity and demonstrated the covalent attachment of [32P]-ADPribose moieties to histones, which are catalyzed by PARP. In further experiments, we demonstrated that C. fasciculata PARP and recombinant TcPARP require no magnesium or any other metal ion cofactor for their activity and are inhibited by typical PARP inhibitors: nicotinamide, 3-aminobenzamide, theophylline and thymidine. TcPARP and TcPARG were localized to the cell nucleus. Our findings demonstrated that covalent poly-ADP-ribosylation of PARP itself or DNA topoisomerase I resulted in the inhibitionof their activities, which were restored after removing the ADP-ribose polymers. DNAdamaging agents, which trigger different repair mechanisms, induce poly-ADP-ribosesynthesis in the nucleus, as was established by our group in epimastigotes of T. cruzi.The role of poly-ADP-ribose metabolism in trypanosomatids remains to be furtherinvestigated, and unraveling it could be important for the development of new therapies against these parasites.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nova Science Publishers, Inc
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
TRYPANOSMATIDS
dc.subject
POLY-ADP-RIBOSE METABOLISM
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.title
Metabolism of Poly-ADP-ribose in Trypanosomatids
dc.type
info:eu-repo/semantics/publishedVersion
dc.type
info:eu-repo/semantics/bookPart
dc.type
info:ar-repo/semantics/parte de libro
dc.date.updated
2020-06-08T16:28:07Z
dc.journal.pagination
119-141
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Georgia
dc.description.fil
Fil: Alonso, Guillermo Daniel. 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: 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: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.novapublishers.org/catalog/product_info.php?products_id=18797
dc.conicet.paginas
260
dc.source.titulo
Parasitology Research Trends
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