42 research outputs found
Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level
We present a generic model for DNA at the base-pair level. We use a variant
of the Gay-Berne potential to represent the stacking energy between neighboring
base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid
harmonic springs with a non-zero spring length. The competition of these two
interactions and the introduction of a simple geometrical constraint leads to a
stacked right-handed B-DNA-like conformation. The mapping of the presented
model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize
the free model parameters so as to reproduce the experimentally known
observables such as persistence lengths, mean and mean squared base-pair step
parameters. For the optimized model parameters we measured the critical force
where the transition from B- to S-DNA occurs to be approximately . We
observe an overstretched S-DNA conformation with highly inclined bases that
partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR
Centromere behavior during interphase and meiotic prophase in Allium fistulosum from 3-D, E.M. reconstruction
Nopp140-chaperoned 2'-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity
Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB)-specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at ∼80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2'-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.SCOPUS: ar.jinfo:eu-repo/semantics/publishe