title: Glyceraldehyde 3-phosphate dehydrogenase-telomere association correlates with redox status in Trypanosoma cruzi.
abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a classical metabolic enzyme involved in energy production and plays a role in additional nuclear functions, including transcriptional control, recognition of misincorporated nucleotides in DNA and maintenance of telomere structure. Here, we show that the recombinant protein T. cruzi GAPDH (rTcGAPDH) binds single-stranded telomeric DNA. We demonstrate that the binding of GAPDH to telomeric DNA correlates with the balance between oxidized and reduced forms of nicotinamide adenine dinucleotides (NAD+/NADH). We observed that GAPDH-telomere association and NAD+/NADH balance changed throughout the T. cruzi life cycle. For example, in replicative epimastigote forms of T. cruzi, which show similar intracellular concentrations of NAD+ and NADH, GAPDH binds to telomeric DNA in vivo and this binding activity is inhibited by exogenous NAD+. In contrast, in the T. cruzi non-proliferative trypomastigote forms, which show higher NAD+ concentration, GAPDH was absent from telomeres. In addition, NAD+ abolishes physical interaction between recombinant GAPDH and synthetic telomere oligonucleotide in a cell free system, mimicking exogenous NAD+ that reduces GAPDH-telomere interaction in vivo. We propose that the balance in the NAD+/NADH ratio during T. cruzi life cycle homeostatically regulates GAPDH telomere association, suggesting that in trypanosomes redox status locally modulates GAPDH association with telomeric DNA.
authors.affiliation: Laboratório Especial de Ciclo Celular, Instituto Butantan, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, São Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pariona-Llanos
authors.affiliation: Laboratório Especial de Ciclo Celular, Instituto Butantan, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, São Paulo, Brazil.
authors.forename: Raphael Souza
authors.initials: RS
authors.lastname: Pavani
authors.affiliation: Laboratório Especial de Ciclo Celular, Instituto Butantan, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, São Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Reis
authors.affiliation: Laboratório Especial de Ciclo Celular, Instituto Butantan, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, São Paulo, Brazil.
authors.forename: Vincent
authors.initials: V
authors.lastname: Noël
authors.affiliation: Unit for Drug Discovery-Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ariel Mariano
authors.initials: AM
authors.lastname: Silber
authors.affiliation: Laboratório Especial de Ciclo Celular, Instituto Butantan, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, São Paulo, Brazil; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Hugo Aguirre
authors.initials: HA
authors.lastname: Armelin
authors.affiliation: Departamento de Genética, Instituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho-UNESP, Botucatu, Brazil.
authors.forename: Maria Isabel Nogueira
authors.initials: MI
authors.lastname: Cano
authors.affiliation: Laboratório Especial de Ciclo Celular, Instituto Butantan, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, São Paulo, Brazil.
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Elias
mesh_terms: D021581:Active Transport, Cell Nucleus; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D008962:Models, Theoretical; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D021381:Protein Transport; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D009243:NAD; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases