T. cruzi DNA polymerase beta (Tcpol beta) is phosphorylated in vitro by CK1, CK2 and TcAUK1 leading to the potentiation of its DNA synthesis activity
Maldonado Maldonado, Edio Luis
Rojas, Diego A.
Solari Illescas, Aldo Gerónimo
Cita de ítem
PLoS Negl Trop Dis 15(7): e0009588 - 2021
The unicellular protozoan Trypanosoma cruzi is the causing agent of Chagas disease which
affects several millions of people around the world. The components of the cell signaling
pathways in this parasite have not been well studied yet, although its genome can encode
several components able to transduce the signals, such as protein kinases and phosphatases.
In a previous work we have found that DNA polymerase β (Tcpolβ) can be phosphorylated
in vivo and this modification activates the synthesis activity of the enzyme. Tcpolβ is
kinetoplast-located and is a key enzyme in the DNA base excision repair (BER) system. The
polypeptide possesses several consensus phosphorylation sites for several protein kinases,
however, a direct phosphorylation of those sites by specific kinases has not been reported
yet. Tcpolβ has consensus phosphorylation sites for casein kinase 1 (CK1), casein kinase 2
(CK2) and aurora kinase (AUK). Genes encoding orthologues of those kinases exist in T.
cruzi and we were able to identify the genes and to express them to investigate whether or
no Tcpolβ could be a substrate for in vitro phosphorylation by those kinases. Both CK1 and
TcAUK1 have auto-phosphorylation activities and they are able to phosphorylate Tcpolβ.
CK2 cannot perform auto-phosphorylation of its subunits, however, it was able to phosphorylate
Tcpolβ. Pharmacological inhibitors used to inhibit the homologous mammalian kinases
can also inhibit the activity of T. cruzi kinases, although, at higher concentrations. The phosphorylation
events carried out by those kinases can potentiate the DNA polymerase activity
of Tcpolβ and it is discussed the role of the phosphorylation on the DNA polymerase and
lyase activities of Tcpolβ. Taken altogether, indicates that CK1, CK2 and TcAUK1 can play
an in vivo role regulating the function of Tcpolβ.
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT 1190392
Public Library Science
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Attribution-NonCommercial-NoDerivs 3.0 United States