A novel single alpha-helix DNA-binding domain in CAF-1 promotes gene silencing and DNA damage survival through tetrasome-length DNA selectivity and spacer function
Ruben Rosas,
Rhiannon R Aguilar,
Nina Arslanovic,
Anna Seck,
Duncan J Smith,
Jessica K Tyler,
Mair EA Churchill
Affiliations
Ruben Rosas
Program in Structural Biology and Biochemistry, University of Colorado Anschutz Medical Campus, Aurora, United States
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States; Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, United States
Program in Structural Biology and Biochemistry, University of Colorado Anschutz Medical Campus, Aurora, United States; Department of Pharmacology, University of Colorado School of Medicine, Aurora, United States
The histone chaperone chromatin assembly factor 1 (CAF-1) deposits two nascent histone H3/H4 dimers onto newly replicated DNA forming the central core of the nucleosome known as the tetrasome. How CAF-1 ensures there is sufficient space for the assembly of tetrasomes remains unknown. Structural and biophysical characterization of the lysine/glutamic acid/arginine-rich (KER) region of CAF-1 revealed a 128-Å single alpha-helix (SAH) motif with unprecedented DNA-binding properties. Distinct KER sequence features and length of the SAH drive the selectivity of CAF-1 for tetrasome-length DNA and facilitate function in budding yeast. In vivo, the KER cooperates with the DNA-binding winged helix domain in CAF-1 to overcome DNA damage sensitivity and maintain silencing of gene expression. We propose that the KER SAH links functional domains within CAF-1 with structural precision, acting as a DNA-binding spacer element during chromatin assembly.
