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.

• PMID: 30104407
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Evrin C, Maman JD, Diamante A, Pellegrini L, Labib K

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