 |
|
Title
|
|
The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix.
|
|
|
Authors
|
|
H.Hashimoto,
J.R.Horton,
X.Zhang,
M.Bostick,
S.E.Jacobsen,
X.Cheng.
|
|
|
Ref.
|
|
Nature, 2008,
455,
826-829.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Maintenance methylation of hemimethylated CpG dinucleotides at DNA replication
forks is the key to faithful mitotic inheritance of genomic methylation
patterns. UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is
required for maintenance methylation by interacting with DNA nucleotide
methyltransferase 1 (DNMT1), the maintenance methyltransferase, and with
hemimethylated CpG, the substrate for DNMT1 (refs 1 and 2). Here we present the
crystal structure of the SET and RING-associated (SRA) domain of mouse UHRF1 in
complex with DNA containing a hemimethylated CpG site. The DNA is contacted in
both the major and minor grooves by two loops that penetrate into the middle of
the DNA helix. The 5-methylcytosine has flipped completely out of the DNA helix
and is positioned in a binding pocket with planar stacking contacts,
Watson-Crick polar hydrogen bonds and van der Waals interactions specific for
5-methylcytosine. Hence, UHRF1 contains a previously unknown DNA-binding module
and is the first example of a non-enzymatic, sequence-specific DNA-binding
protein domain to use the base flipping mechanism to interact with DNA.
|
|
|
|