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.

TitleA 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 TypeJournal Article
Year of Publication2023
AuthorsRosas R, Aguilar RR, Arslanovic N, Seck A, Smith DJ, Tyler JK, Churchill MEA
JournalElife
Volume12
Date Published2023 Jul 11
ISSN2050-084X
KeywordsChromatin 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.

DOI10.7554/eLife.83538
Alternate JournalElife
PubMed ID37432722
PubMed Central IDPMC10335832
Grant ListP30 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

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