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Does DNA replication direct locus-specific recombination during host immune evasion by antigenic variation in the African trypanosome?

for adaptive genome change found in other organisms. Antigenic variation; Trypanosome; DNA repair; DNA replication; Variant surface glycoprotein - * Richard McCulloch The genome is the crucible of ... McCulloch 0 1 0 Present Address: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee , Dundee , UK 1 The Wellcome Trust Centre for Molecular Parasitology

Does DNA replication direct locus-specific recombination during host immune evasion by antigenic variation in the African trypanosome?

for adaptive genome change found in other organisms. Antigenic variation; Trypanosome; DNA repair; DNA replication; Variant surface glycoprotein - * Richard McCulloch The genome is the crucible of

Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe

. Campbell Richard McCulloch 0 Equal contributors The Wellcome Trust Centre for Molecular Parasitology, Institute of Infection , Immunity and Inflammation , University of Glasgow , Sir Graeme Davis Building

Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation

Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient ...

Evaluation of Antigens for Development of a Serological Test for Human African Trypanosomiasis

Background Control and elimination of human African trypanosomiasis (HAT) can be accelerated through the use of diagnostic tests that are more accurate and easier to deploy. The goal of this work was to evaluate the immuno-reactivity of antigens and identify candidates to be considered for development of a simple serological test for the detection of Trypanosoma brucei gambiense or ...

Distinct Phenotypes Caused by Mutation of MSH2 in Trypanosome Insect and Mammalian Life Cycle Forms Are Associated with Parasite Adaptation to Oxidative Stress

Background DNA repair mechanisms are crucial for maintenance of the genome in all organisms, including parasites where successful infection is dependent both on genomic stability and sequence variation. MSH2 is an early acting, central component of the Mismatch Repair (MMR) pathway, which is responsible for the recognition and correction of base mismatches that occur during DNA ...

Single molecule analysis of Trypanosoma brucei DNA replication dynamics

Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis of Trypanosoma brucei, the etiological agent of sleeping sickness, localized its replication origins to the boundaries of multigenic transcription units. To better understand genomic replication in this organism, we ...

Trypanosoma brucei homologous recombination is dependent on substrate length and homology, though displays a differential dependence on mismatch repair as substrate length decreases

Rebecca L. Barnes 0 Richard McCulloch 0 0 The Wellcome Centre for Molecular Parasitology,University of Glasgow,Glasgow Biomedical Research Centre,120 University Place , Glasgow ,G12 8TA, UK

Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation

Chris Proudfoot 0 Richard McCulloch 0 0 The Wellcome Centre for Molecular Parasitology, University of Glasgow, Anderson College , 56 Dumbarton Road, Glasgow , G11 6NU, UK In Trypanosoma brucei, DNA

Sequence homology and microhomology dominate chromosomal double-strand break repair in African trypanosomes

Genetic diversity in fungi and mammals is generated through mitotic double-strand break-repair (DSBR), typically involving homologous recombination (HR) or non-homologous end joining (NHEJ). Microhomology-mediated joining appears to serve a subsidiary function. The African trypanosome, a divergent protozoan parasite, relies upon rearrangement of subtelomeric variant surface ...

Identification of ORC1/CDC6-Interacting Factors in Trypanosoma brucei Reveals Critical Features of Origin Recognition Complex Architecture

DNA Replication initiates by formation of a pre-replication complex on sequences termed origins. In eukaryotes, the pre-replication complex is composed of the Origin Recognition Complex (ORC), Cdc6 and the MCM replicative helicase in conjunction with Cdt1. Eukaryotic ORC is considered to be composed of six subunits, named Orc1–6, and monomeric Cdc6 is closely related in sequence to ...

Trypanosoma brucei BRCA2 acts in a life cycle-specific genome stability process and dictates BRC repeat number-dependent RAD51 subnuclear dynamics

Trypanosoma brucei survives in mammals through antigenic variation, which is driven by RAD51-directed homologous recombination of Variant Surface Glycoproteins (VSG) genes, most of which reside in a subtelomeric repository of >1000 silent genes. A key regulator of RAD51 is BRCA2, which in T. brucei contains a dramatic expansion of a motif that mediates interaction with RAD51, ...

Antigenic Variation in Trypanosoma brucei: Joining the DOTs

The survival ofTrypanosoma brucei relies on the sucessive expression of a single surface protein gene from a family of around 1,000 genes. This switching appears to be partly dictated by epigenetic changes in chromatin.