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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Zhang K,Gao Y,Li J,Burgess R,Han J,Liang H,Zhang Z,Liu Y

doi

10.1093/nar/gkw106

subject

Has Abstract

pub_date

2016-06-20 00:00:00

pages

5083-94

issue

11

eissn

0305-1048

issn

1362-4962

pii

gkw106

journal_volume

44

pub_type

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