Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations

Chromatin remodelling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodelling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodelling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome

Understanding the Challenges of Expanding Community Forestry in Northwest Cameroon

The tropical afro-montane forest of the Northwest region is unique and under direct threat from the high population density of the region. Community-based forestry management is an opportunity to sustainably manage the remaining forest fragments. Community forestry was introduced to Cameroon with the legislation of the 1994 Forestry Law. Over two decades later little research has been conducted in the Northwest region of Cameroon. Twenty-four semi-structured interviews were conducted, and samples of forestry records were analyzed as exploratory research that would act as a base for further research. This research found that the tenure of the community over the community forest needed to be strengthened, marginalized populations needed to be empowered to participate, and governance needed to be improved both nationally, and locally. Further research will strengthen these conclusions and help Cameroon, and community forests around the world, be effectively established and managed

Structure of replicating SARS-CoV-2 polymerase

The coronavirus SARS-CoV-2 uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes1–3. Here we present the cryo-electron microscopic structure of the SARS-CoV-2 RdRp in active form, mimicking the replicating enzyme. The structure comprises the viral proteins nsp12, nsp8, and nsp7, and over two turns of RNA template-product duplex. The active site cleft of nsp12 binds the first turn of RNA and mediates RdRp activity with conserved residues. Two copies of nsp8 bind to opposite sides of the cleft and position the second turn of RNA. Long helical extensions in nsp8 protrude along exiting RNA, forming positively charged ‘sliding poles’. These sliding poles can account for the known processivity of the RdRp that is required for replicating the long coronavirus genome3. Our results enable a detailed analysis of the inhibitory mechanisms that underlie the antiviral activity of substances such as remdesivir, a drug for the treatment of coronavirus disease 2019 (COVID-19)4