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protein dna_rna ligands metals Protein-protein interface(s) links
Transcription/DNA-RNA hybrid PDB id
2r7z
Jmol
Contents
Protein chains
1416 a.a. *
1108 a.a. *
266 a.a. *
177 a.a. *
214 a.a. *
84 a.a. *
171 a.a. *
133 a.a. *
119 a.a. *
65 a.a. *
114 a.a. *
46 a.a. *
DNA/RNA
Ligands
CPT
Metals
_ZN ×8
_MG
* Residue conservation analysis
PDB id:
2r7z
Name: Transcription/DNA-RNA hybrid
Title: Cisplatin lesion containing RNA polymerase ii elongation com
Structure: 5'-d( Tp Ap Cp Tp Tp Gup Cp Cp Cp Tp Cp Cp Tp Cp Chain: t. Engineered: yes. 5'-d( Cp Ap Ap Gp Tp Ap G)-3'. Chain: n. Engineered: yes. 5'-r( Up Up Up Gp Ap Gp Gp Ap Gp G)-3'. Chain: p. Engineered: yes.
Source: Synthetic: yes. Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Organism_taxid: 4932
Resolution:
3.80Å     R-factor:   0.215     R-free:   0.240
Authors: G.E.Damsma,A.Alt,F.Brueckner,T.Carell,P.Cramer
Key ref:
G.E.Damsma et al. (2007). Mechanism of transcriptional stalling at cisplatin-damaged DNA. Nat Struct Biol, 14, 1127-1133. PubMed id: 17994106 DOI: 10.1038/nsmb1314
Date:
10-Sep-07     Release date:   20-Nov-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04050  (RPB1_YEAST) -  DNA-directed RNA polymerase II subunit RPB1
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1733 a.a.
1416 a.a.
Protein chain
Pfam   ArchSchema ?
P08518  (RPB2_YEAST) -  DNA-directed RNA polymerase II subunit RPB2
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1224 a.a.
1108 a.a.
Protein chain
Pfam   ArchSchema ?
P16370  (RPB3_YEAST) -  DNA-directed RNA polymerase II subunit RPB3
Seq:
Struc: 		318 a.a.
266 a.a.
Protein chain
Pfam   ArchSchema ?
P20433  (RPB4_YEAST) -  DNA-directed RNA polymerase II subunit RPB4
Seq:
Struc: 		221 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
P20434  (RPAB1_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC1
Seq:
Struc: 		215 a.a.
214 a.a.
Protein chain
Pfam   ArchSchema ?
P20435  (RPAB2_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC2
Seq:
Struc: 		155 a.a.
84 a.a.
Protein chain
Pfam   ArchSchema ?
P34087  (RPB7_YEAST) -  DNA-directed RNA polymerase II subunit RPB7
Seq:
Struc: 		171 a.a.
171 a.a.
Protein chain
Pfam   ArchSchema ?
P20436  (RPAB3_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC3
Seq:
Struc: 		146 a.a.
133 a.a.
Protein chain
Pfam   ArchSchema ?
P27999  (RPB9_YEAST) -  DNA-directed RNA polymerase II subunit RPB9
Seq:
Struc: 		122 a.a.
119 a.a.
Protein chain
Pfam   ArchSchema ?
P22139  (RPAB5_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC5
Seq:
Struc: 		70 a.a.
65 a.a.
Protein chain
Pfam   ArchSchema ?
P38902  (RPB11_YEAST) -  DNA-directed RNA polymerase II subunit RPB11
Seq:
Struc: 		120 a.a.
114 a.a.
Protein chain
Pfam   ArchSchema ?
P40422  (RPAB4_YEAST) -  DNA-directed RNA polymerases I, II, and III subunit RPABC4
Seq:
Struc: 		70 a.a.
46 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.2.7.7.6  - DNA-directed Rna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1)
Nucleoside triphosphate
 + RNA(n)
 = diphosphate
 + RNA(n+1)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     RNA polymerase complex   10 terms 
  Biological process     cellular metabolic process   17 terms 
  Biochemical function     catalytic activity     16 terms  

 

 
    reference    
 
 
DOI no: 10.1038/nsmb1314 Nat Struct Biol 14:1127-1133 (2007)
PubMed id: 17994106  
 
 
Mechanism of transcriptional stalling at cisplatin-damaged DNA.
G.E.Damsma, A.Alt, F.Brueckner, T.Carell, P.Cramer.
 
  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.
 
  Selected figure(s)  
 
Figure 3.
(a,b) Anomalous difference Fourier maps of Pol II elongation complexes B (a) and C (b), contoured at 6 . Model of complex A is shown, viewed from the side. 		Figure 5.
(a) Pol II stalling at the cisplatin lesion (this study), shown as a schematic representation of RNA extension in complex A. The initial RNA (top) corresponds to the unextended RNA of scaffold A. Dashed line represents translocation barrier. The artificial conditions leading to lesion bypass are depicted at the bottom. (b) Pol II stalling at a CPD lesion. Schematic is adapted from reference 8.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2007, 14, 1127-1133) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21346784 D.Brégeon, and P.W.Doetsch (2011).
Transcriptional mutagenesis: causes and involvement in tumour development.
  Nat Rev Cancer, 11, 218-227.  
21504834 E.Czeko, M.Seizl, C.Augsberger, T.Mielke, and P.Cramer (2011).
Iwr1 directs RNA polymerase II nuclear import.
  Mol Cell, 42, 261-266.  
21452186 N.Graf, W.H.Ang, G.Zhu, M.Myint, and S.J.Lippard (2011).
Role of endonucleases XPF and XPG in nucleotide excision repair of platinated DNA and cisplatin/oxaliplatin cytotoxicity.
  Chembiochem, 12, 1115-1123.  
21297364 Y.Abe (2011).
[Safety studies of nanomaterials about intracellular distribution and genotoxicity].
  Yakugaku Zasshi, 131, 215-219.  
20730959 A.Atipairin, B.Canyuk, and A.Ratanaphan (2010).
Cisplatin affects the conformation of apo form, not holo form, of BRCA1 RING finger domain and confers thermal stability.
  Chem Biodivers, 7, 1949-1967.  
20448203 D.Wang, G.Zhu, X.Huang, and S.J.Lippard (2010).
X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct.
  Proc Natl Acad Sci U S A, 107, 9584-9589.
PDB codes: 3m3y 3m4o
19682435 L.Zerzankova, T.Suchankova, O.Vrana, N.P.Farrell, V.Brabec, and J.Kasparkova (2010).
Conformation and recognition of DNA modified by a new antitumor dinuclear PtII complex resistant to decomposition by sulfur nucleophiles.
  Biochem Pharmacol, 79, 112-121.  
20482321 P.Cramer (2010).
Towards molecular systems biology of gene transcription and regulation.
  Biol Chem, 391, 731-735.  
20007604 S.Malik, P.Chaurasia, S.Lahudkar, G.Durairaj, A.Shukla, and S.R.Bhaumik (2010).
Rad26p, a transcription-coupled repair factor, is recruited to the site of DNA lesion in an elongating RNA polymerase II-dependent manner in vivo.
  Nucleic Acids Res, 38, 1461-1477.  
19566097 A.A.Hostetter, E.G.Chapman, and V.J.DeRose (2009).
Rapid cross-linking of an RNA internal loop by the anticancer drug cisplatin.
  J Am Chem Soc, 131, 9250-9257.  
19758983 G.E.Damsma, and P.Cramer (2009).
Molecular basis of transcriptional mutagenesis at 8-oxoguanine.
  J Biol Chem, 284, 31658-31663.  
19560423 J.F.Sydow, F.Brueckner, A.C.Cheung, G.E.Damsma, S.Dengl, E.Lehmann, D.Vassylyev, and P.Cramer (2009).
Structural basis of transcription: mismatch-specific fidelity mechanisms and paused RNA polymerase II with frayed RNA.
  Mol Cell, 34, 710-721.
PDB codes: 3hou 3hov 3how 3hox 3hoy 3hoz
19130897 J.M.Ceruti, M.E.Scassa, M.C.Marazita, A.C.Carcagno, P.F.Sirkin, and E.T.Cánepa (2009).
Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response.
  Int J Biochem Cell Biol, 41, 1344-1353.  
  20046924 R.C.Todd, and S.J.Lippard (2009).
Inhibition of transcription by platinum antitumor compounds.
  Metallomics, 1, 280-291.  
18552824 F.Brueckner, and P.Cramer (2008).
Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation.
  Nat Struct Mol Biol, 15, 811-818.
PDB code: 2vum
18579768 K.S.Lovejoy, R.C.Todd, S.Zhang, M.S.McCormick, J.A.D'Aquino, J.T.Reardon, A.Sancar, K.M.Giacomini, and S.J.Lippard (2008).
cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects.
  Proc Natl Acad Sci U S A, 105, 8902-8907.
PDB code: 3co3
19023283 P.C.Hanawalt, and G.Spivak (2008).
Transcription-coupled DNA repair: two decades of progress and surprises.
  Nat Rev Mol Cell Biol, 9, 958-970.  
18573085 P.Cramer, K.J.Armache, S.Baumli, S.Benkert, F.Brueckner, C.Buchen, G.E.Damsma, S.Dengl, S.R.Geiger, A.J.Jasiak, A.Jawhari, S.Jennebach, T.Kamenski, H.Kettenberger, C.D.Kuhn, E.Lehmann, K.Leike, J.F.Sydow, and A.Vannini (2008).
Structure of eukaryotic RNA polymerases.
  Annu Rev Biophys, 37, 337-352.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.