Cohesin is a ring-shaped protein complex that is capable of embracing DNA. Most of the ring circumference is comprised of the anti-parallel intramolecular coiled coils of the Smc1 and Smc3 proteins, which connect globular head and hinge domains. Smc coiled coil arms contain multiple acetylated and ubiquitylated lysines. To investigate the role of these modifications, we substituted lysines for arginines to mimic the unmodified state and uncovered genetic interaction between the Smc arms. Using scanning force microscopy, we show that wild-type Smc arms associate with each other when the complex is not on DNA. Deacetylation of the Smc1/Smc3 dimers promotes arms' dissociation. Smc arginine mutants display loose packing of the Smc arms and, although they dimerize at the hinges, fail to connect the heads and associate with the DNA. Our findings highlight the importance of a "collapsed ring," or "rod," conformation of cohesin for its loading on the chromosomes.
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http://dx.doi.org/10.1016/j.molcel.2016.08.008 | DOI Listing |
Lancet Infect Dis
January 2025
Ministry of Health, Kampala, Uganda.
Background: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine combined with amodiaquine (SPAQ) effectively protects eligible children from malaria in areas of high and seasonal transmission. However, concerns about parasite resistance to sulfadoxine-pyrimethamine in East and Southern Africa necessitate evaluating alternative drug regimens. This study assessed the effectiveness of SPAQ and dihydroartemisinin-piperaquine for SMC in Uganda.
View Article and Find Full Text PDFLancet Infect Dis
January 2025
Department of Parasitology, Research and Training for Health Science, Université Iba Der Thiam de Thiès, Thiès, Senegal.
Background: In Africa, the scale-up of malaria-control interventions has reduced malaria burden, but progress towards elimination has stalled. Mass drug administration (MDA) is promising as a transmission-reducing strategy, but evidence from low-to-moderate transmission settings is needed. We aimed to assess the safety, coverage, and effect of three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine on Plasmodium falciparum incidence and prevalence in southeast Senegal.
View Article and Find Full Text PDFMuscle Nerve
December 2024
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Introduction/aims: A previous randomized controlled trial showed that guided self-help acceptance and commitment therapy plus standard medical care (ACT+SMC) was superior to standard medical care alone (SMC) for improving quality of life (QoL) and mood at 9-weeks post randomization in a sample of people with muscle disorders (MD). This follow-up study evaluated whether these effects were maintained in the longer term alongside individual patterns of response.
Methods: The original study was a two-arm parallel group randomized controlled trial, which compared ACT+SMC to SMC.
Neuroimage
January 2025
Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
Traumatic brachial plexus lesions (TBPL) can lead to permanent impairment of hand function despite timely brachial plexus surgical treatment. In selected cases with no recovery of hand function, the affected forearm can be amputated and replaced by a bionic hand to regain prehensile function. This cross-sectional study aimed to assess (sub)cortical motor activity and functional connectivity changes after TBPL and bionic reconstruction.
View Article and Find Full Text PDFEMBO J
December 2024
Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, United Kingdom.
Genomes are organised into DNA loops by the Structural Maintenance of Chromosomes (SMC) proteins. SMCs establish functional chromosomal sub-domains for DNA repair, gene expression and chromosome segregation, but how SMC activity is specifically targeted is unclear. Here, we define the molecular mechanism targeting the condensin SMC complex to specific chromosomal regions in budding yeast.
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