2R7Z

Cisplatin lesion containing RNA polymerase II elongation complex

Summary for 2R7Z

• Entry DOI: 10.2210/pdb2r7z/pdb
• Descriptor: 5'-D(*TP*AP*CP*TP*TP*GUP*CP*CP*CP*TP*CP*CP*TP*CP*AP*T)-3', DNA-directed RNA polymerase II subunit RPB7, DNA-directed RNA polymerases I, II, and III subunit RPABC3, ... (18 entities in total)
• Functional Keywords: transferase/dna/rna, dna damage, zinc-finger, dna-binding, phosphorylation, cisplatin lesion, misincorporation, rna polymerase ii, transcription- coupled repair, tcr, arrest, stalling, dna lesion, metal-binding, nuclear protein, transcription bubble, damage recognition, elongation complex, transferase, transcription, transferase-dna-rna complex, transcription-dna-rna hybrid complex, transcription/dna-rna hybrid
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Nucleus: P04050 P38902 P08518 P16370 P20433 P20434 P34087 P20436; Nucleus, nucleolus : P22139 P40422 P27999; Cytoplasm : P20435
• Total number of polymer chains: 15
• Total formula weight: 525499.57

Authors

Damsma, G.E.,Alt, A.,Brueckner, F.,Carell, T.,Cramer, P. (deposition date: 2007-09-10, release date: 2007-11-20, Last modification date: 2024-11-20)

Primary citation

Damsma, G.E.,Alt, A.,Brueckner, F.,Carell, T.,Cramer, P.
Mechanism of transcriptional stalling at cisplatin-damaged DNA.
Nat.Struct.Mol.Biol., 14:1127-1133, 2007

PubMed Abstract: 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.

PubMed: 17994106
DOI: 10.1038/nsmb1314

Experimental method

X-RAY DIFFRACTION (3.8 Å)