Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain

Type 2 DNA topoisomerases (Top2) are critical components of key protein complexes involved in DNA replication, chromosome condensation and segregation, as well as gene transcription. The Top2 were found to be the main targets of anticancer agents, leading to intensive efforts to understand their fun...

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Autores principales: Bedez, Claire, Lotz, Christophe, Batisse, Claire, Broeck, Arnaud Vanden, Stote, Roland H., Howard, Eduardo Ignacio, Pradeau Aubreton, Karine, Ruff, Marc, Lamour, Valérie
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Ciencias Exactas
Física
Biología
DNA topoisomerase 2α
Post-translational modifications
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/100487
https://ri.conicet.gov.ar/11336/89288
http://www.nature.com/articles/s41598-018-27606-8
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-100487
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Física
Biología
DNA topoisomerase 2α
Post-translational modifications
spellingShingle Ciencias Exactas
Física
Biología
DNA topoisomerase 2α
Post-translational modifications
Bedez, Claire
Lotz, Christophe
Batisse, Claire
Broeck, Arnaud Vanden
Stote, Roland H.
Howard, Eduardo Ignacio
Pradeau Aubreton, Karine
Ruff, Marc
Lamour, Valérie
Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
topic_facet Ciencias Exactas
Física
Biología
DNA topoisomerase 2α
Post-translational modifications
description Type 2 DNA topoisomerases (Top2) are critical components of key protein complexes involved in DNA replication, chromosome condensation and segregation, as well as gene transcription. The Top2 were found to be the main targets of anticancer agents, leading to intensive efforts to understand their functional and physiological role as well as their molecular structure. Post-translational modifications have been reported to influence Top2 enzyme activities in particular those of the mammalian Top2α isoform. In this study, we identified phosphorylation, and for the first time, acetylation sites in the human Top2α isoform produced in eukaryotic expression systems. Structural analysis revealed that acetylation sites are clustered on the catalytic domains of the homodimer while phosphorylation sites are located in the C-terminal domain responsible for nuclear localization. Biochemical analysis of the eukaryotic-specific K168 residue in the ATPase domain shows that acetylation affects a key position regulating ATP hydrolysis through the modulation of dimerization. Our findings suggest that acetylation of specific sites involved in the allosteric regulation of human Top2 may provide a mechanism for modulation of its catalytic activity.
format Articulo
Articulo
author Bedez, Claire
Lotz, Christophe
Batisse, Claire
Broeck, Arnaud Vanden
Stote, Roland H.
Howard, Eduardo Ignacio
Pradeau Aubreton, Karine
Ruff, Marc
Lamour, Valérie
author_facet Bedez, Claire
Lotz, Christophe
Batisse, Claire
Broeck, Arnaud Vanden
Stote, Roland H.
Howard, Eduardo Ignacio
Pradeau Aubreton, Karine
Ruff, Marc
Lamour, Valérie
author_sort Bedez, Claire
title Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_short Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_full Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_fullStr Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_full_unstemmed Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain
title_sort post-translational modifications in dna topoisomerase 2α highlight the role of a eukaryote-specific residue in the atpase domain
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/100487
https://ri.conicet.gov.ar/11336/89288
http://www.nature.com/articles/s41598-018-27606-8
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