2r7z
Cisplatin lesion containing RNA polymerase II elongation complexCisplatin lesion containing RNA polymerase II elongation complex
Structural highlights
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 PubMedThe 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 AlsoReferences
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OCA- DNA-directed RNA polymerase
- Saccharomyces cerevisiae
- Alt, A.
- Brueckner, F.
- Carell, T.
- Cramer, P.
- Damsma, G E.
- 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
- Transcription-dna-rna hybrid complex
- Transferase
- Transferase-dna-rna complex
- Transferase/dna/rna
- Zinc-finger