2r7z

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Cisplatin lesion containing RNA polymerase II elongation complexCisplatin lesion containing RNA polymerase II elongation complex

Structural highlights

2r7z is a 15 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Activity:DNA-directed RNA polymerase, with EC number 2.7.7.6
Resources:FirstGlance, OCA, RCSB, PDBsum

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Damsma GE, Alt A, Brueckner F, Carell T, Cramer P. Mechanism of transcriptional stalling at cisplatin-damaged DNA. Nat Struct Mol Biol. 2007 Dec;14(12):1127-33. Epub 2007 Nov 11. PMID:17994106 doi:10.1038/nsmb1314

2r7z, resolution 3.80Å

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