The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones
Year: 2016
Type: article
Abstract: The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 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)2 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.
Source: eLife
DOI: 10.7554/elife.18023
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Macromolecular X-ray Data Collection Instrumentation, ABI Elite ESI-QqTOF Mass Spectrometry System, LTQ Orbitrap Mass Spectrometer Request, G4727808288, Linking Dynamics to Catalysis and Inhibition in ERK2, Quantum 315 r Detector, Colorado Clinical and Translational Sciences Institute, Predoctoral Training in Signaling and Cellular Regulation, G709708941, University of Colorado Cancer Center Support Grant, Predoctoral Training Program in Signaling and Cellular Regulation, G9001225491
OpenAlex ID: W2523872091