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PDBsum entry 4y52
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Transcription/DNA/RNA
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PDB id
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4y52
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Contents |
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1393 a.a.
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1103 a.a.
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266 a.a.
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214 a.a.
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84 a.a.
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133 a.a.
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119 a.a.
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65 a.a.
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114 a.a.
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45 a.a.
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References listed in PDB file
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Key reference
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Title
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Molecular basis for 5-Carboxycytosine recognition by RNA polymerase ii elongation complex.
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Authors
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L.Wang,
Y.Zhou,
L.Xu,
R.Xiao,
X.Lu,
L.Chen,
J.Chong,
H.Li,
C.He,
X.D.Fu,
D.Wang.
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Ref.
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Nature, 2015,
523,
621-625.
[DOI no: ]
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PubMed id
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Abstract
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DNA methylation at selective cytosine residues (5-methylcytosine (5mC)) and
their removal by TET-mediated DNA demethylation are critical for setting up
pluripotent states in early embryonic development. TET enzymes successively
convert 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and
5-carboxylcytosine (5caC), with 5fC and 5caC subject to removal by thymine DNA
glycosylase (TDG) in conjunction with base excision repair. Early reports
indicate that 5fC and 5caC could be stably detected on enhancers, promoters and
gene bodies, with distinct effects on gene expression, but the mechanisms have
remained elusive. Here we determined the X-ray crystal structure of yeast
elongating RNA polymerase II (Pol II) in complex with a DNA template containing
oxidized 5mCs, revealing specific hydrogen bonds between the 5-carboxyl group of
5caC and the conserved epi-DNA recognition loop in the polymerase. This causes a
positional shift for incoming nucleoside 5'-triphosphate (NTP), thus
compromising nucleotide addition. To test the implication of this structural
insight in vivo, we determined the global effect of increased 5fC/5caC levels on
transcription, finding that such DNA modifications indeed retarded Pol II
elongation on gene bodies. These results demonstrate the functional impact of
oxidized 5mCs on gene expression and suggest a novel role for Pol II as a
specific and direct epigenetic sensor during transcription elongation.
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