Title | 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 | Journal Article |
Year of Publication | 2023 |
Authors | Rosas R, Aguilar RR, Arslanovic N, Seck A, Smith DJ, Tyler JK, Churchill MEA |
Journal | Elife |
Volume | 12 |
Date Published | 2023 Jul 11 |
ISSN | 2050-084X |
Keywords | Chromatin Assembly Factor-1, DNA, DNA Damage, Gene Silencing, Histones, Molecular Chaperones, Protein Conformation, alpha-Helical |
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 |
Alternate Journal | Elife |
PubMed ID | 37432722 |
PubMed Central ID | PMC10335832 |
Grant List | P30 CA046934 / CA / NCI NIH HHS / United States R01 CA095641 / CA / NCI NIH HHS / United States R01 GM064475 / GM / NIGMS NIH HHS / United States S10 OD012033 / OD / NIH HHS / United States R35 GM134918 / GM / NIGMS NIH HHS / United States R35 GM139816 / GM / NIGMS NIH HHS / United States R01 GM135604 / GM / NIGMS NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by bel2021 on February 16, 2024 - 10:35am