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In recent years, a great interest has been focused on the prebiotic origin of nucleic acids and life on Earth. An attractive idea is that life was initially based on an autocatalytic and autoreplicative RNA (the RNA-world). RNA duplexes are right-handed helical chains with antiparallel orientation, but the rationale for these features is not yet known.

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Despite the sequencing revolution, large swaths of the genomes sequenced to date lack any information about the arrangement of transcription factor binding sites on regulatory DNA. Massively Parallel Reporter Assays (MPRAs) have the potential to dramatically accelerate our genomic annotations by making it possible to measure the gene expression levels driven by thousands of mutational variants of a regulatory region. However, the interpretation of such data often assumes that each base pair in a regulatory sequence contributes independently to gene expression.

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Cellular chromatin displays heterogeneous structure and dynamics, properties that control diverse nuclear processes. Models invoke phase separation of conformational ensembles of chromatin fibers as a mechanism regulating chromatin organization . Here we combine biochemistry and molecular dynamics simulations to examine, at single base-pair resolution, how nucleosome spacing controls chromatin phase separation.

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Insights into the behaviour of phosphorylated DNA breaks from molecular dynamic simulations.

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December 2024

Faculty of Biochemistry and Molecular Medicine, University of Oulu, PO Box 5400, Oulu 90014, Finland; Biocenter Oulu, University of Oulu, PO Box 5400, Oulu 90014, Finland. Electronic address:

Single-stranded breaks (SSBs) are the most frequent DNA lesions threatening genomic integrity-understanding how DNA sensor proteins recognize certain SSB types is crucial for studies of the DNA repair pathways. During repair of damaged DNA the final SSB that is to be ligated contains a 5'-phosphorylated end. The present work employed molecular simulation (MD) of DNA with a phosphorylated break in solution to address multiple questions regarding the dynamics of the break site.

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This study explored the genomic alterations in , a key yeast in industrial biotechnology, under both spontaneous and mutagen-induced conditions. Our findings reveal that spontaneous mutations occur at a rate of approximately 4 × 10 events per base pair per cell division, primarily manifesting as single-nucleotide variations (SNVs) and small insertions and deletions (InDels). Notably, C-to-T/G-to-A transitions and C-to-A/G-to-T transversions dominate the spontaneous SNVs, while 1 bp deletions, likely resulting from template slippage, are the most frequent InDels.

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