A DNA binding winged helix domain in CAF-1 functions with PCNA to stabilize CAF-1 at replication forks

Nucleic Acids Research
Kuo ZhangYingfang Liu

Abstract

Chromatin assembly factor 1 (CAF-1) is a histone H3-H4 chaperone that deposits newly synthesized histone (H3-H4)2 tetramers during replication-coupled nucleosome assembly. However, how CAF-1 functions in this process is not yet well understood. Here, we report the crystal structure of C terminus of Cac1 (Cac1C), a subunit of yeast CAF-1, and the function of this domain in stabilizing CAF-1 at replication forks. We show that Cac1C forms a winged helix domain (WHD) and binds DNA in a sequence-independent manner. Mutations in Cac1C that abolish DNA binding result in defects in transcriptional silencing and increased sensitivity to DNA damaging agents, and these defects are exacerbated when combined with Cac1 mutations deficient in PCNA binding. Similar phenotypes are observed for corresponding mutations in mouse CAF-1. These results reveal a mechanism conserved in eukaryotic cells whereby the ability of CAF-1 to bind DNA is important for its association with the DNA replication forks and subsequent nucleosome assembly.

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Citations

Apr 19, 2017·Scientific Reports·Francesca MattiroliKarolin Luger
Feb 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ryan JankeJasper Rine
Oct 5, 2017·Nucleic Acids Research·Varun KumarPeter P Nawroth
Sep 6, 2018·Annual Review of Genetics·Prerna GroverEric I Campos
Jul 12, 2017·Frontiers in Genetics·Hollie RowlandsKrassimir Yankulov
May 2, 2019·The Journal of Biological Chemistry·M Daniel RickettsRonen Marmorstein
Apr 25, 2019·Essays in Biochemistry·Alonso J PardalAndrew J Bowman
Mar 20, 2020·Cell & Bioscience·Wenshuo ZhangQing Li

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