A DNA binding winged helix domain in CAF-1 functions with PCNA to stabilize CAF-1 at replication forks
Copyright policy )A DNA binding winged helix domain in CAF-1 functions with PCNA to stabilize CAF-1 at replication forks
Chromatin assembly factor 1 (CAF-1) is a histone H3-H4 chaperone that deposits newly synthesized histone (H3-H4)2 tetramers during replication-coupled nucleosome assembly. However, how CAF-1 functions in this process is not yet well understood. Here, we report the crystal structure of C terminus of Cac1 (Cac1C), a subunit of yeast CAF-1, and the function of this domain in stabilizing CAF-1 at replication forks. We show that Cac1C forms a winged helix domain (WHD) and binds DNA in a sequence-independent manner. Mutations in Cac1C that abolish DNA binding result in defects in transcriptional silencing and increased sensitivity to DNA damaging agents, and these defects are exacerbated when combined with Cac1 mutations deficient in PCNA binding. Similar phenotypes are observed for corresponding mutations in mouse CAF-1. These results reveal a mechanism conserved in eukaryotic cells whereby the ability of CAF-1 to bind DNA is important for its association with the DNA replication forks and subsequent nucleosome assembly.
- Sichuan University China (People's Republic of)
- Mayo Clinic United States
- Mayo Clinic United States
- State Key Laboratory of Biomacromolecules China (People's Republic of)
- Institute of Biophysics China (People's Republic of)
DNA Replication, Models, Molecular, Protein Conformation, Recombinant Fusion Proteins, Gene regulation, Chromatin and Epigenetics, Replication Origin, Histones, Chromatin Assembly Factor-1, Mice, Structure-Activity Relationship, Proliferating Cell Nuclear Antigen, Mutation, Animals, Nucleic Acid Conformation, Protein Interaction Domains and Motifs, Protein Binding
DNA Replication, Models, Molecular, Protein Conformation, Recombinant Fusion Proteins, Gene regulation, Chromatin and Epigenetics, Replication Origin, Histones, Chromatin Assembly Factor-1, Mice, Structure-Activity Relationship, Proliferating Cell Nuclear Antigen, Mutation, Animals, Nucleic Acid Conformation, Protein Interaction Domains and Motifs, Protein Binding
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