Replication dynamics of recombination-dependent replication forks
Autor: | Eduard Campillo-Funollet, Adam T. Watson, Antony M. Carr, Karel Naiman, Izumi Miyabe, Alice Budden |
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Rok vydání: | 2020 |
Předmět: |
DNA Replication
0301 basic medicine QR0001 Software_OPERATINGSYSTEMS Science Genetic stability MathematicsofComputing_NUMERICALANALYSIS General Physics and Astronomy Context (language use) DNA-Directed DNA Polymerase Article General Biochemistry Genetics and Molecular Biology Resection 03 medical and health sciences 0302 clinical medicine TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY Schizosaccharomyces Replication (statistics) Homologous chromosome Homologous Recombination Communication and replication QH581.2 Polymerase Physics Multidisciplinary biology Chemistry Dynamics (mechanics) DNA replication General Chemistry Cell biology 030104 developmental biology ComputingMethodologies_PATTERNRECOGNITION biology.protein Schizosaccharomyces pombe Proteins Homologous recombination 030217 neurology & neurosurgery Recombination MathematicsofComputing_DISCRETEMATHEMATICS Single strand |
Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) Nature Communications |
ISSN: | 2041-1723 |
Popis: | Replication forks restarted by homologous recombination are error prone and replicate both strands semi-conservatively using Pol δ. Here, we use polymerase usage sequencing to visualize in vivo replication dynamics of HR-restarted forks at an S. pombe replication barrier, RTS1, and model replication by Monte Carlo simulation. We show that HR-restarted forks synthesise both strands with Pol δ for up to 30 kb without maturing to a δ/ε configuration and that Pol α is not used significantly on either strand, suggesting the lagging strand template remains as a gap that is filled in by Pol δ later. We further demonstrate that HR-restarted forks progress uninterrupted through a fork barrier that arrests canonical forks. Finally, by manipulating lagging strand resection during HR-restart by deleting pku70, we show that the leading strand initiates replication at the same position, signifying the stability of the 3′ single strand in the context of increased resection. Replication forks that are stalled at obstacles on the DNA template can be restarted by homologous recombination. Here, the authors show replication dynamics during homologous recombination-dependent replication fork restart by combining polymerase usage sequencing and a Monte Carlo mathematical model. |
Databáze: | OpenAIRE |
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