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.
| Publication Type | Academic Article |
| Authors | Rosas R, Aguilar R, Arslanovic N, Seck A, Smith D, Tyler J, Churchill M |
| Journal | Elife |
| Volume | 12 |
| Date Published | 07/11/2023 |
| ISSN | 2050-084X |
| Keywords | DNA, DNA Damage |
| Abstract | 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. |
| DOI | 10.7554/eLife.83538 |
| PubMed ID | 37432722 |
| PubMed Central ID | PMC10335832 |