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PDBsum entry 3av6
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References listed in PDB file
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Key reference
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Title
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Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (dnmt1).
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Authors
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K.Takeshita,
I.Suetake,
E.Yamashita,
M.Suga,
H.Narita,
A.Nakagawa,
S.Tajima.
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Ref.
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Proc Natl Acad Sci U S A, 2011,
108,
9055-9059.
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PubMed id
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Abstract
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Methylation of cytosine in DNA plays a crucial role in development through
inheritable gene silencing. The DNA methyltransferase Dnmt1 is responsible for
the propagation of methylation patterns to the next generation via its
preferential methylation of hemimethylated CpG sites in the genome; however, how
Dnmt1 maintains methylation patterns is not fully understood. Here we report the
crystal structure of the large fragment (291-1620) of mouse Dnmt1 and its
complexes with cofactor S-adenosyl-L-methionine and its product
S-adenosyl-L-homocystein. Notably, in the absence of DNA, the N-terminal domain
responsible for targeting Dnmt1 to replication foci is inserted into the
DNA-binding pocket, indicating that this domain must be removed for methylation
to occur. Upon binding of S-adenosyl-L-methionine, the catalytic cysteine
residue undergoes a conformation transition to a catalytically competent
position. For the recognition of hemimethylated DNA, Dnmt1 is expected to
utilize a target recognition domain that overhangs the putative DNA-binding
pocket. Taking into considerations the recent report of a shorter fragment
structure of Dnmt1 that the CXXC motif positions itself in the catalytic pocket
and prevents aberrant de novo methylation, we propose that maintenance
methylation is a multistep process accompanied by structural changes.
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