University of Oulu

Haikarainen, T., Schlesinger, M., Obaji, E., Fernández Villamil, S., Lehtiö, L. (2017) Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei . Scientific Reports, 7 (1), . doi:DOI:10.1038/s41598-017-03751-4

Structural and Biochemical Characterization of Poly-ADP-ribose Polymerase from Trypanosoma brucei

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Author: Haikarainen, Teemu1,2; Schlesinger, Mariana3; Obaji, Ezeogo1,2;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, University of Oulu, FI-90014, Oulu, Finland
2Biocenter Oulu, University of Oulu, FI-90014, Oulu, Finland
3National Institute for Genetic Engineering and Molecular Biology (INGEBI-CONICET), University of Buenos Aires, Buenos Aires, Argentina
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.1 MB)
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Language: English
Published: Nature Publishing Group, 2017
Publish Date: 2017-06-21


Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T. brucei PARP. T. brucei PARP was found to be selectively activated by 5′ phosphorylated and 3′ phosphorylated DNA breaks. Importantly, the N-terminal region is responsible for high-affinity DNA-binding and required for DNA-dependent enzymatic activation. This module is also required for nuclear localization of the protein in response to oxidative stress. Solution structures of activating and non-activating PARP-DNA complexes were determined with small-angle X-ray scattering revealing distinct differences in their DNA-binding modes.
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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 7
Issue: 1
Article number: 3642
DOI: 10.1038/s41598-017-03751-4
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was funded by Biocenter Oulu, Academy of Finland (grant No. 287063 and 294085 for LL and grant No. 266922 for TH) and Sigrid Jusélius Foundation. This work was supported by Agencia Nacional de Promoción Científica y Tecnológica (Argentina), Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Universidad de Buenos Aires (Argentina) and EMBO Short Term Fellowship. MS is a fellow of the CONICET. Small-angle X-ray scattering experiments were performed at ESRF (Grenoble, France) on beamline BM29. We are grateful to Local Contacts at ESRF for providing assistance in using the beamline. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under BioStruct-X (Grant agreement No. 283570). The use of the facilities of the Biocenter Oulu Proteomics and protein analysis core facility is gratefully acknowledged.
EU Grant Number: (283570) BIOSTRUCT-X - Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities
Academy of Finland Grant Number: 287063
Detailed Information: 287063 (Academy of Finland Funding decision)
294085 (Academy of Finland Funding decision)
266922 (Academy of Finland Funding decision)
Dataset Reference: Supplementary information accompanies this paper at doi:10.1038/s41598-017-03751-4
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