Producción CyT
Artículo
Autoría
Bedez, Claire
;
Lotz, Christophe
;
Batisse, Claire
;
Broeck, Arnaud Vanden
;
Stote, Roland H.
;
Howard, Eduardo Ignacio
;
Pradeau-Aubreton, Karine
;
Ruff, Marc
;
Lamour, Valérie
Fecha
2018
Editorial y Lugar de Edición
Nature Publishing Group
Revista
Scientific Reports,
vol. 8
- ISSN 2045-2322
Nature Publishing Group
Nature Publishing Group
ISSN
2045-2322
Resumen
Información suministrada por el agente en
SIGEVA
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 Top2?...
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 Top2? isoform. In this study, we identified phosphorylation, and for the first time, acetylation sites in the human Top2? 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.
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Palabras Clave
POST-TRANSLATIONAL MODIFICATIONSDNA TOPOISOMERASE 2?
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