The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones

The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4) histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 arch...

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Bibliographic Details
Published in:eLife 2016-09, Vol.5
Main Authors: Liu, Wallace H, Roemer, Sarah C, Zhou, Yeyun, Shen, Zih-Jie, Dennehey, Briana K, Balsbaugh, Jeremy L, Liddle, Jennifer C, Nemkov, Travis, Ahn, Natalie G, Hansen, Kirk C, Tyler, Jessica K, Churchill, Mair Ea
Format: Article
Language:English
Subjects:
Architecture
Biochemistry
Biophysics and Structural Biology
C-Terminus
Chromatin remodeling
Deoxyribonucleic acid
DNA
DNA biosynthesis
Experiments
Genes and Chromosomes
histone chaperone
Histones
Laboratories
mass spectrometry
Mass spectroscopy
Medicine
Molecular chaperones
Nucleosome
Observations
Peptides
Physiological aspects
Protein interaction
Protein-protein interactions
Proteins
Replication
structural biology
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Summary:The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4) histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex. Cac1 alone not only binds H3/H4 with high affinity, but also promotes histone tetramerization independent of the other subunits. Moreover, we identify a minimal region in the C-terminus of Cac1, including the structured winged helix domain and glutamate/aspartate-rich domain, which is sufficient to induce (H3/H4) tetramerization. These findings reveal a key role of Cac1 in histone tetramerization, providing a new model for CAF-1-H3/H4 architecture and function during eukaryotic replication.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.18023