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PDBsum entry 2r7z
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Transcription/DNA-RNA hybrid
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PDB id
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2r7z
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Contents |
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1416 a.a.
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1108 a.a.
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266 a.a.
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177 a.a.
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214 a.a.
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84 a.a.
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171 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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46 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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Mechanism of transcriptional stalling at cisplatin-Damaged DNA.
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Authors
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G.E.Damsma,
A.Alt,
F.Brueckner,
T.Carell,
P.Cramer.
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Ref.
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Nat Struct Biol, 2007,
14,
1127-1133.
[DOI no: ]
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PubMed id
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Abstract
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The anticancer drug cisplatin forms 1,2-d(GpG) DNA intrastrand cross-links
(cisplatin lesions) that stall RNA polymerase II (Pol II) and trigger
transcription-coupled DNA repair. Here we present a structure-function analysis
of Pol II stalling at a cisplatin lesion in the DNA template. Pol II stalling
results from a translocation barrier that prevents delivery of the lesion to the
active site. AMP misincorporation occurs at the barrier and also at an abasic
site, suggesting that it arises from nontemplated synthesis according to an
'A-rule' known for DNA polymerases. Pol II can bypass a cisplatin lesion that is
artificially placed beyond the translocation barrier, even in the presence of a
G.A mismatch. Thus, the barrier prevents transcriptional mutagenesis. The
stalling mechanism differs from that of Pol II stalling at a photolesion, which
involves delivery of the lesion to the active site and lesion-templated
misincorporation that blocks transcription.
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Figure 3.
(a,b) Anomalous difference Fourier maps of Pol II elongation
complexes B (a) and C (b), contoured at 6  .
Model of complex A is shown, viewed from the side.
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Figure 5.
(a) Pol II stalling at the cisplatin lesion (this study),
shown as a schematic representation of RNA extension in complex
A. The initial RNA (top) corresponds to the unextended RNA of
scaffold A. Dashed line represents translocation barrier. The
artificial conditions leading to lesion bypass are depicted at
the bottom. (b) Pol II stalling at a CPD lesion. Schematic is
adapted from reference 8.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
1127-1133)
copyright 2007.
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