Evidence for cohesin sliding along budding yeast chromosomes

The ring-shaped cohesin complex is thought to topologically hold sister chromatids together from their synthesis in S phase until chromosome segregation in mitosis. How cohesin stably binds to chromosomes for extended periods, without impeding other chromosomal processes that also require access to the DNA, is poorly understood. Budding yeast cohesin is loaded onto DNA by the Scc2–Scc4 cohesin loader at centromeres and promoters of active genes, from where cohesin translocates to more permanent places of residence at transcription termination sites. Here we show that, at the GAL2 and MET17 loci, pre-existing cohesin is pushed downstream along the DNA in response to transcriptional gene activation, apparently without need for intermittent dissociation or reloading. We observe translocation intermediates and find that the distribution of most chromosomal cohesin is shaped by transcription. Our observations support a model in which cohesin is able to slide laterally along chromosomes while maintaining topological contact with DNA. In this way, stable cohesin binding to DNA and enduring sister chromatid cohesion become compatible with simultaneous underlying chromosomal activities, including but maybe not limited to transcription

Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing

How different organs in the body sense growth perturbations in distant tissues to coordinatetheir size during development is poorly understood. Here we mutate an invertebrate orphanrelaxin receptor gene, the Drosophila Leucine-rich repeat-containing G protein-coupled receptor 3(Lgr3), and find body asymmetries similar to those found in insulin-like peptide 8 (dilp8)mutants, which fail to coordinate growth with developmental timing. Indeed, mutation or RNAintereference (RNAi) against Lgr3 suppresses the delay in pupariation induced by imaginaldisc growth perturbation or ectopic Dilp8 expression. By tagging endogenous Lgr3 andperforming cell type-specific RNAi, we map this Lgr3 activity to a new subset of CNS neurons,four of which are a pair of bilateral pars intercerebralis Lgr3-positive (PIL) neurons that respondspecifically to ectopic Dilp8 by increasing cAMP-dependent signalling. Our work sheds newlight on the function and evolution of relaxin receptors and reveals a novel neuroendocrinecircuit responsive to growth aberrations.Fil: Garelli, Andres. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Heredia, Fabiana. Nova University of Lisbon. CEDOC-Chronic Diseases Research Center; PortugalFil: Casimiro, Andreia P.. Nova University of Lisbon. CEDOC-Chronic Diseases Research Center; PortugalFil: Macedo, Andre. Nova University of Lisbon. CEDOC-Chronic Diseases Research Center; PortugalFil: Nunes, Catarina. Nova University of Lisbon. CEDOC-Chronic Diseases Research Center; PortugalFil: Garcez, Marcia. Nova University of Lisbon. CEDOC-Chronic Diseases Research Center; PortugalFil: Mantas Dias, Angela R.. Nova University of Lisbon. CEDOC-Chronic Diseases Research Center; PortugalFil: Volonté, Yanel Andrea. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Uhlmann, Thomas. Dualsystems Biotech Ag; SuizaFil: Caparros, Esther. Universidad Miguel Hernández. Facultad de Medicina; EspañaFil: Koyama, Takashi. Instituto Gulbenkian de Ciência; PortugalFil: Gontijo, Alisson M.. Nova University of Lisbon. CEDOC-Chronic Diseases Research Center; Portuga