RESEARCH ARTICLE DNA-mediated association of two histone-bound complexes of yeast Chromatin Assembly Factor-1 (CAF-1) drives tetrasome assembly in the wake of DNA replication Francesca Mattiroli1*†, Yajie Gu1,2†, Tejas Yadav3,4, Jeremy L Balsbaugh5, Michael R Harris4, Eileen S Findlay1, Yang Liu1, Catherine A Radebaugh2, Laurie A Stargell2,6, Natalie G Ahn7, Iestyn Whitehouse4, Karolin Luger1,6* 1Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States; 2Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, United States; 3Weill Cornell Graduate School of Medical Sciences, New York, United States; 4Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States; 5Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, United States; 6Institute for Genome Architecture and Function, Colorado State University, Fort Collins, United States; 7Biofrontiers Institute, University of Colorado Boulder, Boulder, United States *For correspondence: francesca. Abstract Nucleosome assembly in the wake of DNA replication is a key process that regulates
[email protected] (FM); cell identity and survival. Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that
[email protected] (KL) associates with the replisome and orchestrates chromatin assembly following DNA synthesis. Little is known about the mechanism and structure of this key complex. Here we investigate the CAF- †These authors contributed 1.H3-H4 binding mode and the mechanism of nucleosome assembly. We show that yeast CAF-1 equally to this work binding to a H3-H4 dimer activates the Cac1 winged helix domain interaction with DNA. This drives Competing interests: The the formation of a transient CAF-1.histone.DNA intermediate containing two CAF-1 complexes, authors declare that no each associated with one H3-H4 dimer.