Histone H2A-H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin.

Abstract

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.

• Authors: Cecile Evrin, Joseph D Maman, Aurora Diamante, Luca Pellegrini, Karim Labib
• Journal: The EMBO journal (EMBO J) Vol. 37 Issue 19 (10 01 2018) ISSN: 1460-2075 [Electronic] England
• PMID: 30104407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Chemical References

• Chromatin
• DNA-Binding Proteins
• FACT protein, S cerevisiae
• High Mobility Group Proteins
• Histones
• Saccharomyces cerevisiae Proteins
• Transcriptional Elongation Factors
• DNA Polymerase I
• MCM2 protein, S cerevisiae

Topics

• Chromatin (genetics, metabolism)
• DNA Polymerase I (genetics, metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• High Mobility Group Proteins (genetics, metabolism)
• Histones (metabolism)
• Humans
• Saccharomyces cerevisiae (genetics, metabolism)
• Saccharomyces cerevisiae Proteins (genetics, metabolism)
• Transcriptional Elongation Factors (genetics, metabolism)