About this Research Topic
All organisms require a competent cellular machinery to replicate their DNA or RNA genomes accurately between successive generations. Errors of replication and chemical lesions or physical obstacles to replication progression are frequent, and require correction. Failure to do so triggers genome instability that takes many guises, including genetic re-arrangements and base mutations that are enabling characteristics for cancers.
Cells have evolved multiple pathways to overcome the various problems encountered by active replication forks, guarding against genome instability. These include repair strategies based on the complementarity of DNA sequences around the problem (e.g. homologous recombination in several forms), direct DNA lesion removal machineries (e.g. excision repair), and DNA end-joining mechanisms. These various DNA/RNA repair processes utilize multi-protein complexes to catalyze the diverse reactions required, including nucleic acid unwinding (helicases/topoisomerases), synthesis (polymerases), degradation (exo-/endonucleases), and joining (ligases). In addition, multiple regulating proteins are often required to deliver or remove post-translational protein modifications. Furthermore, these DNA/RNA repair processes underpin other major cellular processes, including naturally occurring prokaryotic CRISPR immunity systems and the use of CRISPR genetic editing technology.
The advent of advanced structural biology methods has illuminated at the atomic, molecular and cellular scales the molecular mechanisms of proteins in replication, recombination, and repair pathways. Structural biology greatly complements traditional biochemical, biophysical, and cell biological studies of these pathways, elucidating how replication and repair enzymes modify their nucleic acid substrates, and also how they interact with one another in doing so. Such knowledge is critical in assisting the development of chemotherapeutic approaches towards combating human cancers and, of particular topical interest, towards anti-viral strategies targeting Ebola and SARS-CoV-2.
This Research Topic aims to collate original research, review, and perspective articles relating to the structural biology of nucleic acid replication, recombination, and repair in viruses, prokaryotes, and eukaryotes. This includes (but is not restricted to) both high and low resolution approaches including: Cryogenic electron microscopy (cryo-EM), macromolecular X-ray crystallography (MX), nuclear magnetic resonance (NMR), small angle X-ray scattering (SAXS), mass spectrometry (MS), single molecule techniques, molecular dynamics/modelling, and integrative approaches combining multiple methods with biophysical techniques such as analytical ultracentrifugation (AUC) and light scattering (SEC-MALLS).
Keywords: DNA replication, DNA recombination, DNA repair, CRISPR, chemotherapy, DNA polymerase, helicase, ligase, exonuclease, endonuclease, structural biology, NMR, X-ray crystallography, cryo-EM, SAXS, mass spectrometry, molecular dynamics, molecular modelling
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