Physiological Chemistry

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The parasite Trypanosoma brucei causes sleeping sickness. It evades human defences by changing the version of a protein that coats its surface. In this paper the group of Nicolai Siegel report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding. Genome-wide chromosome conformation capture reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. more

The activity of the human oncogene and chromatin remodeler ALC1 is strictly regulated by PARP1 activation. In this new study we reveal how oligomers of ADP-ribose trigger the activation of ALC1 from an auto-inhibited state. We identify cancer mutations that disrupt the NAD+-metabolite-regulated allosteric mechanism and activate chromatin remodeling. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation. more