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

Nucleic Acids Res. 2018 Nov 2;46(19):9907-9917. doi: 10.1093/nar/gky823.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Chromatin Assembly Factor-1 / physiology*
  • Chromatin Assembly and Disassembly / physiology*
  • Histones / metabolism*
  • Humans
  • Molecular Chaperones / metabolism
  • Nucleosomes / metabolism*

Substances

  • Chromatin
  • Chromatin Assembly Factor-1
  • Histones
  • Molecular Chaperones
  • Nucleosomes