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PDBsum entry 3fde
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References listed in PDB file
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Key reference
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Title
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Uhrf1, A modular multi-Domain protein, Regulates replication-Coupled crosstalk between DNA methylation and histone modifications.
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Authors
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H.Hashimoto,
J.R.Horton,
X.Zhang,
X.Cheng.
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Ref.
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Epigenetics, 2009,
4,
8.
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PubMed id
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Abstract
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Cytosine methylation in DNA is a major epigenetic signal, and plays a central
role in propagating chromatin status during cell division. However the
mechanistic links between DNA methylation and histone methylation are poorly
understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and
RING finger domains 1) is required for DNA CpG maintenance methylation at
replication forks, and mouse UHRF1-null cells show enhanced susceptibility to
DNA replication arrest and DNA damaging agents. Recent data demonstrated that
the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and
flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and
PHD domain bind the tail of histone H3 in a highly methylation sensitive manner.
We hypothesize that UHRF1 brings the two components (histones and DNA) carrying
appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to
be assembled into a nucleosome after replication.
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Secondary reference #1
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Title
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The sra domain of uhrf1 flips 5-Methylcytosine out of the DNA helix.
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Authors
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H.Hashimoto,
J.R.Horton,
X.Zhang,
M.Bostick,
S.E.Jacobsen,
X.Cheng.
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Ref.
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Nature, 2008,
455,
826-829.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1: Structure of SRA–DNA complex. a, Summary of the
SRA–DNA interactions; mc, main-chain-atom-mediated contacts;
w, water-mediated hydrogen bonds. Black boxes represent CpG
recognition sequence and K495-associated dotted lines represent
weak hydrogen bonds. b, The side chains of V451 of the base
flipping loop and R496 of the CpG recognition loop are in direct
van der Waals contact. c, The two loops—CpG recognition and
base flipping—penetrate into the DNA helix from opposite
directions. d, The 5mC flips out and binds in a cage-like
pocket. e, The surface charge at neutral pH is displayed as blue
for positive (20 k[B]T), red for negative (-20 k[B]T), and white
for neutral, where k[B] is the Boltzmann's constant and T is the
temperature.
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Figure 2.
Figure 2: Details of SRA–DNA interactions. a, The 5mC  G
base pair is shown in the front, and the adjoining G C
base pair is in the back. b, Planar stacking contacts of the
extrahelical 5mC with Y471 and Y483 (left image). Omit electron
densities, contoured at 4  and
5 above
the mean, respectively, are shown for omitting 5mC (blue) or the
methyl group (red) (right image). c, The hydrogen bond
interactions with the polar atoms of 5mC. The double-dotted
lines indicate van der Waals contacts with the methyl group of
ring carbon C5. d, H450 forms a hydrogen bond from the minor
groove side with cytosine of G C
pair at position 5 (see Fig. 1a). e, Network of internal polar
interactions centred on residues H447 and S464. Gua, guanine. f,
Network of internal charged interactions centred on residues
R541 and D560. Distances are shown in angstroms.
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The above figures are
reproduced from the cited reference
which is an Open Access publication published by Macmillan Publishers Ltd
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