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bioRxiv · 10.1101/2022.10.11.511754

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

Rosas, R.·Aguilar, R. R.·Arslanovic, N.·Tyler, J. K.·Churchill, M. E. A.
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Abstract

The histone chaperone chromatin assembly factor 1 (CAF-1) deposits 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 [A] 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.

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Rosas, R., Aguilar, R. R., Arslanovic, N., Tyler, J. K., Churchill, M. E. A.. 2022-10-11. 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. https://doi.org/10.1101/2022.10.11.511754

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