2r7z
From Proteopedia
(New page: 200px<br /><applet load="2r7z" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r7z, resolution 3.80Å" /> '''Cisplatin lesion con...) |
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==Overview== | ==Overview== | ||
| - | The anticancer drug cisplatin forms 1,2-d(GpG) DNA intrastrand cross-links | + | 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. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Mechanism of transcriptional stalling at cisplatin-damaged DNA., Damsma GE, Alt A, Brueckner F, Carell T, Cramer P, Nat Struct Mol Biol. 2007 Nov 11 | + | Mechanism of transcriptional stalling at cisplatin-damaged DNA., Damsma GE, Alt A, Brueckner F, Carell T, Cramer P, Nat Struct Mol Biol. 2007 Dec;14(12):1127-33. Epub 2007 Nov 11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17994106 17994106] |
[[Category: DNA-directed RNA polymerase]] | [[Category: DNA-directed RNA polymerase]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Carell, T.]] | [[Category: Carell, T.]] | ||
[[Category: Cramer, P.]] | [[Category: Cramer, P.]] | ||
| - | [[Category: Damsma, G | + | [[Category: Damsma, G E.]] |
[[Category: CPT]] | [[Category: CPT]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:45:16 2008'' |
Revision as of 16:45, 21 February 2008
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Cisplatin lesion containing RNA polymerase II elongation complex
Overview
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.
About this Structure
2R7Z is a Protein complex structure of sequences from Saccharomyces cerevisiae with , and as ligands. Active as DNA-directed RNA polymerase, with EC number 2.7.7.6 Full crystallographic information is available from OCA.
Reference
Mechanism of transcriptional stalling at cisplatin-damaged DNA., Damsma GE, Alt A, Brueckner F, Carell T, Cramer P, Nat Struct Mol Biol. 2007 Dec;14(12):1127-33. Epub 2007 Nov 11. PMID:17994106
Page seeded by OCA on Thu Feb 21 18:45:16 2008
Categories: DNA-directed RNA polymerase | Protein complex | Saccharomyces cerevisiae | Alt, A. | Brueckner, F. | Carell, T. | Cramer, P. | Damsma, G E. | CPT | MG | ZN | Arrest | Cisplatin lesion | Damage recognition | Dna damage | Dna lesion | Dna-binding | Elongation complex | Metal-binding | Misincorporation | Nuclear protein | Phosphorylation | Rna polymerase ii | Stalling | Tcr | Transcription | Transcription bubble | Transcription- coupled repair | Transferase | Transferase/dna/rna | Transferase/dna/rna complex | Zinc-finger
