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

Kuo Zhang, Yuan Gao, Jingjing Li, Rebecca Burgess, Junhong Han, Huanhuan Liang, Zhiguo Zhang, Yingfang Liu

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5083-5094
Number of pages12
JournalNucleic acids research
Volume44
Issue number11
DOIs
StatePublished - Jun 20 2016

ASJC Scopus subject areas

  • Genetics

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    Zhang, K., Gao, Y., Li, J., Burgess, R., Han, J., Liang, H., Zhang, Z., & Liu, Y. (2016). A DNA binding winged helix domain in CAF-1 functions with PCNA to stabilize CAF-1 at replication forks. Nucleic acids research, 44(11), 5083-5094. https://doi.org/10.1093/nar/gkw106