Ortholog of the polymerase theta helicase domain modulates DNA replication in Trypanosoma cruzi

Scientific Reports
Loyze P de LimaM Carolina Elias

Abstract

DNA polymerase theta (Polθ), a member of the DNA polymerase family A, exhibits a polymerase C-terminal domain, a central domain, and an N-terminal helicase domain. Polθ plays important roles in DNA repair via its polymerase domain, regulating genome integrity. In addition, in mammals, Polθ modulates origin firing timing and MCM helicase recruitment to chromatin. In contrast, as a model eukaryote, Trypanosoma cruzi exhibits two individual putative orthologs of Polθ in different genomic loci; one ortholog is homologous to the Polθ C-terminal polymerase domain, and the other is homologous to the Polθ helicase domain, called Polθ-polymerase and Polθ-helicase, respectively. A pull-down assay using the T. cruzi component of the prereplication complex Orc1/Cdc6 as bait captured Polθ-helicase from the nuclear extract. Orc1/Cdc6 and Polθ-helicase directly interacted, and Polθ-helicase presented DNA unwinding and ATPase activities. A T. cruzi strain overexpressing the Polθ-helicase domain exhibited a significantly decreased amount of DNA-bound MCM7 and impaired replication origin firing. Taken together, these data suggest that Polθ-helicase modulates DNA replication by directly interacting with Orc1/Cdc6, which reduces the binding of MCM...Continue Reading

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Citations

Feb 23, 2021·Parasitology·Ester PolákováVyacheslav Yurchenko

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Methods Mentioned

BETA
pull-down
pull down
helicase
flow cytometry
PCR
transfection

Software Mentioned

Mascot Science
ProteoWizard
MSConvert
BLASTP
AttuneTM NxT
BLAST
Polθ
GraphPad
Mascot
ImageJ

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