MCM2 binding to histones H3–H4 and ASF1 supports a tetramer-to-dimer model for histone inheritance at the replication fork

Abstract

587 helicase complex. This suggests that the interaction of MCM2 with histones involving a tetramer-to-dimer transition is important for the proper function of the replication machinery. The work provides a molecular framework coordinating histone H3–H4 recycling with replication-fork progression. Finally, after finding that MCM2 binds all H3 variants (H3.1, H3.2, H3.3 and CENP-A), the authors proposed that this mechanism to handle histones probably applies throughout the entire genome. MCM2 binding to histones was discovered almost 20 years ago7. The hypothesis that the histones H2A–H2B in a nucleosome core particle. In the second mode, MCM2 binds a dimer of H3–H4 engaged in an interaction with the ASF1 histone chaperone. The first structure is consistent with the recent report from Richet et al.3. The second configuration relies on the capacity of the histone chaperone ASF1 to disrupt the histone tetramer4–6. Importantly, the authors identified key point mutations in MCM2 that prevent complex formation and impede cell proliferation in vivo. Notably, point mutants in the histonebinding surface of MCM2 also disrupt binding to CDC45, a component of the active During DNA replication, the replication machinery acts on a chromatin template. The resultant challenge is two-fold: ahead of the fork, nucleosomal organization must be disrupted to allow the machinery to progress; behind the fork, the newly synthesized DNA must be repackaged. Histones, the protein fabric of the nucleosome, cycle through disruption of nucleosomes, recycling and de novo deposition (Fig. 1). In principle, for each nucleosome disrupted by fork progression, the cell must supply two in order to reproduce an equivalent nucleosomal density on the replicated daughter chromatids. This supply involves both recycling of parental histones and deposition of new histones1. How this choreography of histones at the replication fork is orchestrated has been a long-standing puzzle. A key question is whether the recycling of parental histones involves the direct transfer of a tetramer or its splitting into two dimers. In this issue, Patel, Groth and colleagues explored how MCM2, a key subunit of the replicative helicase, binds to H3–H4 (ref. 2). Their structural analysis shows two binding modes. In the first mode, MCM2 binds an H3–H4 tetramer by replacing both DNA and MCM2 binding to histones H3–H4 and ASF1 supports a tetramer-to-dimer model for histone inheritance at the replication fork

DOI: 10.1038/nsmb.3067
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@article{Clment2015MCM2BT, title={MCM2 binding to histones H3–H4 and ASF1 supports a tetramer-to-dimer model for histone inheritance at the replication fork}, author={Camille Cl{\'e}ment and Genevi{\`e}ve Almouzni}, journal={Nature Structural &Molecular Biology}, year={2015}, volume={22}, pages={587-589} }