Histone H2A-H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin.
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Evrin, C., Maman, J. D., Diamante, A., Pellegrini, L., & Labib, K. (2018). Histone H2A-H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin.. EMBO J, 37 (19) https://doi.org/10.15252/embj.201899021
The eukaryotic replisome disassembles parental chromatin at DNA replication forks, but then plays a poorly understood role in the re-deposition of the displaced histone complexes onto nascent DNA. Here, we show that yeast DNA polymerase α contains a histone-binding motif that is conserved in human Pol α and is specific for histones H2A and H2B. Mutation of this motif in budding yeast cells does not affect DNA synthesis, but instead abrogates gene silencing at telomeres and mating-type loci. Similar phenotypes are produced not only by mutations that displace Pol α from the replisome, but also by mutation of the previously identified histone-binding motif in the CMG helicase subunit Mcm2, the human orthologue of which was shown to bind to histones H3 and H4. We show that chromatin-derived histone complexes can be bound simultaneously by Mcm2, Pol α and the histone chaperone FACT that is also a replisome component. These findings indicate that replisome assembly unites multiple histone-binding activities, which jointly process parental histones to help preserve silent chromatin during the process of chromosome duplication.
Chromatin, Humans, Saccharomyces cerevisiae, DNA Polymerase I, DNA-Binding Proteins, Saccharomyces cerevisiae Proteins, High Mobility Group Proteins, Histones, Transcriptional Elongation Factors
Wellcome Trust (104641/Z/14/Z)
External DOI: https://doi.org/10.15252/embj.201899021
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285812
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/