CUL-2^LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis

Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2(LRR-1) associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2(LRR1) as a key regulated step during DNA replication termination. Interestingly, however, CMG persists on chromatin until prophase in worms that lack CUL-2(LRR-1), but is then removed by a mitotic pathway that requires the CDC-48 cofactor UBXN-3, orthologous to the human tumour suppressor FAF1. Partial inactivation of lrr-1 and ubxn-3 leads to synthetic lethality, suggesting future approaches by which a deeper understanding of CMG disassembly in metazoa could be exploited therapeutically

Thinking and Doing: Challenge, Agency, and the Eudaimonic Experience in Video Games

The nascent growth of videogames has led to great leaps in technical understanding in how to create a functional and entertaining play experience. However, the complex, mixed-affect, eudaimonic entertainment experience that is possible when playing a video game—how it is formed, how it is experienced and how to design for it, has been investigated far less than hedonistic emotional experiences focusing on fun, challenge and ‘enjoyment.’ Participants volunteered to be interviewed about their mixed-affect emotional experiences of playing avant-garde videogames. New conceptions of agency emerged (Actual, Interpretive, Fictional, Mechanical) from the analysis of transcripts and were used to produce a framework of four categories of agency. This new framework offers designers and researchers the extra nuance in conversations around agency, and contributes to the discussion of how we can design video games that allow for complex, reflective, eudaimonic emotional experiences

Research Horizons [Volume 25, Number 3, Summer 2008]

NOTE: This PDF file was created from original HTML files on GTRI's website. The file may contain contain links to URIs outside of SMARTech. The Georgia Tech Library and Information Center cannot guarantee the authenticity of resources that reside outside the smartech.gatech.edu domain.COVER STORY: Systems Biology -- FEATURES: Magnetic Control; Fuel Efficiency; Tornado Tally; Innovation at the Coast; Reducing Noise; Evolution and Ecology; Worm Sorter; Fate of Nanoparticles -- DEPARTMENTS: Research in the News; Awards and Honors; Research Notes

An insulin-like peptide regulates egg maturation and metabolism in the mosquito Aedes aegypti

Ingestion of vertebrate blood is essential for egg maturation and transmission of disease-causing parasites by female mosquitoes. Prior studies with the yellow fever mosquito, Aedes aegypti, indicated blood feeding stimulates egg production by triggering the release of hormones from medial neurosecretory cells in the mosquito brain. The ability of bovine insulin to stimulate a similar response further suggested this trigger is an endogenous insulin-like peptide (ILP). A. aegypti encodes eight predicted ILPs. Here, we report that synthetic ILP3 dose-dependently stimulated yolk uptake by oocytes and ecdysteroid production by the ovaries at lower concentrations than bovine insulin. ILP3 also exhibited metabolic activity by elevating carbohydrate and lipid storage. Binding studies using ovary membranes indicated that ILP3 had an IC50 value of 5.9 nM that was poorly competed by bovine insulin. Autoradiography and immunoblotting studies suggested that ILP3 binds the mosquito insulin receptor (MIR), whereas loss-of-function experiments showed that ILP3 activity requires MIR expression. Overall, our results identify ILP3 as a critical regulator of egg production by A. aegypti