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Related Concept Videos

The Replisome03:01

The Replisome

DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
Chromosome Replication02:31

Chromosome Replication

Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin of...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The DNA Replication Fork01:02

The DNA Replication Fork

An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication forks, one in...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...

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Updated: May 31, 2026

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
09:19

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes

Published on: July 22, 2014

Trypanosome prereplication machinery: a potential new target for an old problem.

Simone Guedes Calderano1, Patricia Diogo de Melo Godoy, Julia Pinheiro Chagas da Cunha

  • 1Laboratório Especial de Toxinologia Aplicada (LETA) Center for Applied Toxinology (CAT/CEPID), Instituto Butantan, Avenida Vital Brasil 1500, 05503-000 São Paulo, SP, Brazil.

Enzyme Research
|July 15, 2011
PubMed
Summary

Trypanosome Orc1/Cdc6, crucial for DNA replication, is a promising drug target for Chagas disease and sleeping sickness. Silencing this protein in Trypanosoma brucei proved lethal, highlighting its essential role in parasite survival.

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High-throughput Gene Tagging in Trypanosoma brucei
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Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome
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Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome

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Last Updated: May 31, 2026

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
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High-throughput Gene Tagging in Trypanosoma brucei
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High-throughput Gene Tagging in Trypanosoma brucei

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Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome
05:22

Electrophoretic Analysis of Replication Through Structure-Prone DNA Repeats Within the SV40-Based Human Episome

Published on: September 13, 2024

Area of Science:

  • Parasitology
  • Molecular Biology
  • Drug Discovery

Background:

  • Chagas disease (Trypanosoma cruzi) and sleeping sickness (Trypanosoma brucei) affect millions globally, primarily in Latin America and sub-Saharan Africa.
  • Current treatments for these neglected tropical diseases are limited by toxicity and variable efficacy against different parasite strains and disease stages.
  • Novel therapeutic targets are urgently needed to combat these debilitating protozoan infections.

Purpose of the Study:

  • To identify and validate new drug targets for trypanosomal diseases.
  • To investigate the essentiality of the prereplication machinery component Orc1/Cdc6 in trypanosomes.

Main Methods:

  • Comparative analysis of trypanosome Orc1/Cdc6 with its mammalian counterparts.
  • RNA interference (RNAi)-mediated gene silencing of Orc1/Cdc6 in Trypanosoma brucei.

Main Results:

  • Trypanosome Orc1/Cdc6 exhibits distinct structural and functional characteristics compared to mammalian Orc1 and Cdc6.
  • Suppression of Orc1/Cdc6 expression via RNAi led to a significant decrease in Trypanosoma brucei cell survival.
  • Orc1/Cdc6 plays a critical role in nuclear DNA replication and is essential for trypanosome viability.

Conclusions:

  • The trypanosome Orc1/Cdc6 protein represents a potential and validated drug target for developing new therapies against Chagas disease and sleeping sickness.
  • Targeting Orc1/Cdc6 offers a promising strategy to overcome limitations of existing treatments for these neglected tropical diseases.