Publications by authors named "Craig Lapsley"
Article Synopsis
- * In African trypanosomes, a specific process called targeted recombination helps them evade host immunity by activating one out of many silent variant genes, with unclear mechanisms behind it.
- * The enzyme RAD51 interacts with RNA-DNA hybrids and is crucial for repairing DNA breaks, with mutations in RAD51 affecting the abundance of these hybrids and disrupting the repair related to immune evasion strategies.
DNA replication is needed to duplicate a cell's genome in S phase and segregate it during cell division. Previous work in detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase. Here, we show that acetylated histone H3 (AcH3), base J and a kinetochore factor co-localise in each chromosome at only a single locus, which corresponds with previously mapped DNA replication initiation regions and is demarcated by localised G/T skew and G4 patterns.
View Article and Find Full Text PDFHomologous recombination (HR) has an intimate relationship with genome replication, both during repair of DNA lesions that might prevent DNA synthesis and in tackling stalls to the replication fork. Recent studies led us to ask if HR might have a more central role in replicating the genome of Leishmania, a eukaryotic parasite. Conflicting evidence has emerged regarding whether or not HR genes are essential, and genome-wide mapping has provided evidence for an unorthodox organisation of DNA replication initiation sites, termed origins.
View Article and Find Full Text PDFArticle Synopsis
- Trypanosoma brucei, a parasite, avoids the host's immune response by frequently changing its surface proteins, specifically the variant surface glycoprotein (VSG), through a process called recombination.
- The study reveals that a protein kinase known as ATR is critical for maintaining genomic stability and regulating VSG expression; its loss results in increased VSG switching and instability.
- This research highlights ATR's dual role in enabling the parasite to manage DNA damage while controlling which VSGs are expressed on its surface, contributing to its ability to evade the immune system.
Article Synopsis
- * Loss of RNase H2 (TbRH2A) in the parasite Trypanosoma brucei results in growth arrest and nuclear damage due to problems at RNA polymerase II transcription sites, highlighting its critical role.
- * Although overall RNA levels remain stable after losing TbRH2A, there's significant disruption in nucleotide metabolic genes and an accumulation of R-loops and DNA damage at telomeric sites, suggesting different but overlapping roles for RNase H enzymes in various transcription processes.
Article Synopsis
- Switching the Variant Surface Glycoprotein (VSG) is a key strategy used by Trypanosoma brucei to evade the host's immune response, facilitated by transcription and recombination processes within specialized expression sites.
- The study identifies that RNA-DNA hybrids, known as R-loops, form in the actively expressed VSG site and can also spread to inactive sites when the enzyme RNase H1, which typically degrades these hybrids, is absent.
- The absence of RNase H1 not only increases VSG switching but also causes genome damage, suggesting that the structure of VSG expression sites plays a crucial role in both immune evasion and the formation of R-loops.
Article Synopsis
- * The study maps R-loops in both wild type and RNase H1 mutant T. brucei, finding them at key genomic locations such as centromeres and rRNA genes, indicating some conserved functions despite unusual transcription mechanisms without traditional promoter motifs.
- * The research suggests that R-loops are primarily associated with pre-mRNA processing rather than transcription termination, as they are most abundant in non-coding regions of multigene units linked to polyadenylation and nucleosome-depletion, with little
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.
View Article and Find Full Text PDFHomologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues.
View Article and Find Full Text PDFIntergenerational effects arise when parents' actions influence the reproduction and survival of their offspring and possibly later descendants. Models suggest that intergenerational effects have important implications for both population dynamical patterns and the evolution of life-history traits. However, these will depend on the nature and duration of intergenerational effects.
View Article and Find Full Text PDFThe well studied trade-off between offspring size and offspring number assumes that offspring fitness increases with increasing per-offspring investment. Where mothers differ genetically or exhibit plastic variation in reproductive effort, there can be variation in per capita investment in offspring, and via this trade-off, variation in fecundity. Variation in per capita investment will affect juvenile performance directly--a classical maternal effect--while variation in fecundity will also affect offspring performance by altering the offsprings' competitive environment.
View Article and Find Full Text PDFIn most organisms, transitions between different life-history stages occur later and at smaller sizes as growth conditions deteriorate. Day and Rowe recently proposed that this pattern could be explained by the existence of developmental thresholds (minimum sizes or levels of condition below which transitions are unable to proceed). The developmental-threshold model predicts that the reaction norm of age and size at maturity will rotate in an anticlockwise manner from positive to a shallow negative slope if: (i) initial body size or condition is reduced; and/or (ii) some individuals encounter poor growth conditions at increasingly early developmental stages.
View Article and Find Full Text PDFIn variable environments, it is probable that environmental conditions in the past can influence demographic performance now. Cohort effects occur when these delayed life-history effects are synchronized among groups of individuals in a population. Here we show how plasticity in density-dependent demographic traits throughout the life cycle can lead to cohort effects and that there can be substantial population dynamic consequences of these effects.
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