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Mechanistic insights into histone deposition and nucleosome assembly by the chromatin assembly factor-1.

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journal contribution
posted on 2019-07-03, 15:58 authored by PV Sauer, Y Gu, WH Liu, F Mattiroli, D Panne, K Luger, MEA Churchill
Eukaryotic chromatin is a highly dynamic structure with essential roles in virtually all DNA-dependent cellular processes. Nucleosomes are a barrier to DNA access, and during DNA replication, they are disassembled ahead of the replication machinery (the replisome) and reassembled following its passage. The Histone chaperone Chromatin Assembly Factor-1 (CAF-1) interacts with the replisome and deposits H3-H4 directly onto newly synthesized DNA. Therefore, CAF-1 is important for the establishment and propagation of chromatin structure. The molecular mechanism by which CAF-1 mediates H3-H4 deposition has remained unclear. However, recent studies have revealed new insights into the architecture and stoichiometry of the trimeric CAF-1 complex and how it interacts with and deposits H3-H4 onto substrate DNA. The CAF-1 trimer binds to a single H3-H4 dimer, which induces a conformational rearrangement in CAF-1 promoting its interaction with substrate DNA. Two CAF-1•H3-H4 complexes co-associate on nucleosome-free DNA depositing (H3-H4)2 tetramers in the first step of nucleosome assembly. Here, we review the progress made in our understanding of CAF-1 structure, mechanism of action, and how CAF-1 contributes to chromatin dynamics during DNA replication.

Funding

National Institutes of Health (NIH) [R01GM111902 to M.E.A.C.]; Howard Hughes Medical Institute (to K.L., Y.G. and F.M.); European Molecular Biology Organization [ALTF 1267-2013 to F.M.]; The Dutch Cancer Society [KWF 2014-6649 to F.M.]; The ANR Grant ‘Replicaf' [ANR-16-CE11-0028-02 to D.P.]. Funding for open access charge: NIH.

History

Citation

Nucleic Acids Research, 2018, 46(19), pp. 9907–9917

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

  • VoR (Version of Record)

Published in

Nucleic Acids Research

Publisher

Oxford University Press (OUP)

eissn

1362-4962

Acceptance date

2018-09-15

Copyright date

2018

Available date

2019-07-03

Publisher version

https://academic.oup.com/nar/article/46/19/9907/5099446

Language

en

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