2r7z | pdb_00002r7z

File:2r7z.gif

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2r7z, resolution 3.80Å
Ligands:	CPT, ZN and MG
Activity:	DNA-directed RNA polymerase, with EC number 2.7.7.6
Coordinates:	save as pdb, mmCIF, xml

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. 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

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