Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation.

Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating - a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility.

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

BACKGROUND: DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania. RESULTS: Origin mapping in Leishmania suggests a striking divergence in origin usage relative to characterized eukaryotes, since each chromosome appears to be replicated from a single origin. By comparing two species of Leishmania, we find evidence that such origin singularity is maintained in the face of chromosome fusion or fission events during evolution. Mapping Leishmania origins suggests that all origins fire with equal efficiency, and that the genomic sites occupied by origins differ from related non-origins sites. Finally, we provide evidence that origin location in Leishmania displays striking conservation with Trypanosoma brucei, despite the latter parasite replicating its chromosomes from multiple, variable strength origins. CONCLUSIONS: The demonstration of chromosome replication for a single origin in Leishmania, a microbial eukaryote, has implications for the evolution of origin multiplicity and associated controls, and may explain the pervasive aneuploidy that characterizes Leishmania chromosome architecture.

The effects of distraction and a brief intervention on auditory and visual-spatial working memory in college students with attention deficit hyperactivity disorder.

Two studies addressed how young adult college students with attention deficit hyperactivity disorder (ADHD) (n = 44) compare to their nonaffected peers (n = 42) on tests of auditory and visual-spatial working memory (WM), are vulnerable to auditory and visual distractions, and are affected by a simple intervention. Students with ADHD demonstrated worse auditory WM than did controls. A near significant trend indicated that auditory distractions interfered with the visual WM of both groups and that, whereas controls were also vulnerable to visual distractions, visual distractions improved visual WM in the ADHD group. The intervention was ineffective. Limited correlations emerged between self-reported ADHD symptoms and objective test performances; students with ADHD who perceived themselves as more symptomatic often had better WM and were less vulnerable to distractions than their ADHD peers.