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PDBsum entry 2bcs

Go to PDB code: 
protein dna_rna ligands metals links
Transferase, lyase/DNA PDB id
2bcs
Jmol
Contents
Protein chain
324 a.a. *
DNA/RNA
Ligands
PPV
Metals
_MG
_NA ×2
Waters ×269
* Residue conservation analysis
PDB id:
2bcs
Name: Transferase, lyase/DNA
Title: DNA polymerase lambda in complex with a DNA duplex containing an unpaired dcmp
Structure: 5'-d( Gp Cp Cp G)-3'. Chain: d. Engineered: yes. Other_details: template. 5'-d( Cp Ap Gp Tp Ap Cp G)-3'. Chain: p. Engineered: yes. Other_details: primer. 5'-d( Cp Gp Gp Cp Cp Gp Cp Tp Ap Cp Tp G)-3'.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.20Å     R-factor:   0.207     R-free:   0.241
Authors: M.Garcia-Diaz,K.Bebenek,J.M.Krahn,L.C.Pedersen,T.A.Kunkel
Key ref:
M.Garcia-Diaz et al. (2006). Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase. Cell, 124, 331-342. PubMed id: 16439207 DOI: 10.1016/j.cell.2005.10.039
Date:
19-Oct-05     Release date:   07-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9UGP5  (DPOLL_HUMAN) -  DNA polymerase lambda
Seq:
Struc:
 
Seq:
Struc:
575 a.a.
324 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.7.7  - DNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Deoxynucleoside triphosphate
+ DNA(n)
=
diphosphate
Bound ligand (Het Group name = PPV)
corresponds exactly
+ DNA(n+1)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     DNA repair   1 term 
  Biochemical function     DNA binding     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.cell.2005.10.039 Cell 124:331-342 (2006)
PubMed id: 16439207  
 
 
Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase.
M.Garcia-Diaz, K.Bebenek, J.M.Krahn, L.C.Pedersen, T.A.Kunkel.
 
  ABSTRACT  
 
Insertions and deletions in coding sequences can alter the reading frame of genes and have profound biological consequences. In 1966, Streisinger proposed that these mutations result from strand slippage, which in repetitive sequences generates misaligned intermediates stabilized by correct base pairing that support polymerization. We report here crystal structures of human DNA polymerase lambda, which frequently generates deletion mutations, bound to such intermediates. Each contains an extrahelical template nucleotide upstream of the active site. Surprisingly, the extra nucleotide, even when combined with an adjacent mismatch, does not perturb polymerase active site geometry, which is indistinguishable from that for correctly aligned strands. These structures reveal how pol lambda can polymerize on substrates with minimal homology during repair of double-strand breaks and represent strand-slippage intermediates consistent with Streisinger's classical hypothesis. They are thus relevant to the origin of single-base deletions, a class of mutations that can confer strong biological phenotypes.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. The Extrahelical Adenine Is in Close Proximity to β strand 8
Figure 4.
Figure 4. Pol λ Can Tolerate Distortion upstream of the Primer Terminus
 
  The above figures are reprinted by permission from Cell Press: Cell (2006, 124, 331-342) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21429821 A.L.Abdulovic, S.E.Hile, T.A.Kunkel, and K.A.Eckert (2011).
The in vitro fidelity of yeast DNA polymerase δ and polymerase ɛ holoenzymes during dinucleotide microsatellite DNA synthesis.
  DNA Repair (Amst), 10, 497-505.  
21233421 K.Bebenek, L.C.Pedersen, and T.A.Kunkel (2011).
Replication infidelity via a mismatch with Watson-Crick geometry.
  Proc Natl Acad Sci U S A, 108, 1862-1867.
PDB codes: 3pml 3pmn 3pnc
21377475 P.Xie (2011).
A model for the dynamics of mammalian family X DNA polymerases.
  J Theor Biol, 277, 111-122.  
20975951 A.Demogines, A.M.East, J.H.Lee, S.R.Grossman, P.C.Sabeti, T.T.Paull, and S.L.Sawyer (2010).
Ancient and recent adaptive evolution of primate non-homologous end joining genes.
  PLoS Genet, 6, e1001169.  
19631767 J.Yamtich, and J.B.Sweasy (2010).
DNA polymerase family X: function, structure, and cellular roles.
  Biochim Biophys Acta, 1804, 1136-1150.  
20435673 K.Bebenek, M.Garcia-Diaz, R.Z.Zhou, L.F.Povirk, and T.A.Kunkel (2010).
Loop 1 modulates the fidelity of DNA polymerase lambda.
  Nucleic Acids Res, 38, 5419-5431.
PDB codes: 3mgh 3mgi
19933314 K.Takakusagi, Y.Takakusagi, K.Ohta, S.Aoki, F.Sugawara, and K.Sakaguchi (2010).
A sulfoglycolipid beta-sulfoquinovosyldiacylglycerol (betaSQDG) binds to Met1-Arg95 region of murine DNA polymerase lambda (Mmpol lambda) and inhibits its nuclear transit.
  Protein Eng Des Sel, 23, 51-60.  
20154704 O.Rechkoblit, A.Kolbanovskiy, L.Malinina, N.E.Geacintov, S.Broyde, and D.J.Patel (2010).
Mechanism of error-free and semitargeted mutagenic bypass of an aromatic amine lesion by Y-family polymerase Dpo4.
  Nat Struct Mol Biol, 17, 379-388.
PDB codes: 3khg 3khh 3khl 3khr
19502493 F.Romain, I.Barbosa, J.Gouge, F.Rougeon, and M.Delarue (2009).
Conferring a template-dependent polymerase activity to terminal deoxynucleotidyltransferase by mutations in the Loop1 region.
  Nucleic Acids Res, 37, 4642-4656.  
20064374 F.Wang, and W.Yang (2009).
Structural insight into translesion synthesis by DNA Pol II.
  Cell, 139, 1279-1289.
PDB codes: 3k57 3k58 3k59 3k5a 3k5l 3k5m 3k5n 3k5o 3maq
19572669 M.C.Foley, and T.Schlick (2009).
Relationship between conformational changes in pol lambda's active site upon binding incorrect nucleotides and mismatch incorporation rates.
  J Phys Chem B, 113, 13035-13047.  
19701199 M.Garcia-Diaz, K.Bebenek, A.A.Larrea, J.M.Havener, L.Perera, J.M.Krahn, L.C.Pedersen, D.A.Ramsden, and T.A.Kunkel (2009).
Template strand scrunching during DNA gap repair synthesis by human polymerase lambda.
  Nat Struct Mol Biol, 16, 967-972.  
19835416 M.Urban, N.Joubert, M.Hocek, R.E.Alexander, and R.D.Kuchta (2009).
Herpes simplex virus-1 DNA primase: a remarkably inaccurate yet selective polymerase.
  Biochemistry, 48, 10866-10881.  
19155277 W.A.Baase, D.Jose, B.C.Ponedel, P.H.von Hippel, and N.P.Johnson (2009).
DNA models of trinucleotide frameshift deletions: the formation of loops and bulges at the primer-template junction.
  Nucleic Acids Res, 37, 1682-1689.  
17881298 J.M.Daley, and T.E.Wilson (2008).
Evidence that base stacking potential in annealed 3' overhangs determines polymerase utilization in yeast nonhomologous end joining.
  DNA Repair (Amst), 7, 67-76.  
18503084 M.E.Arana, M.Seki, R.D.Wood, I.B.Rogozin, and T.A.Kunkel (2008).
Low-fidelity DNA synthesis by human DNA polymerase theta.
  Nucleic Acids Res, 36, 3847-3856.  
17159995 A.F.Moon, M.Garcia-Diaz, K.Bebenek, B.J.Davis, X.Zhong, D.A.Ramsden, T.A.Kunkel, and L.C.Pedersen (2007).
Structural insight into the substrate specificity of DNA Polymerase mu.
  Nat Struct Mol Biol, 14, 45-53.
PDB code: 2ihm
17631059 A.F.Moon, M.Garcia-Diaz, V.K.Batra, W.A.Beard, K.Bebenek, T.A.Kunkel, S.H.Wilson, and L.C.Pedersen (2007).
The X family portrait: structural insights into biological functions of X family polymerases.
  DNA Repair (Amst), 6, 1709-1725.  
17095011 K.A.Fiala, J.A.Brown, H.Ling, A.K.Kshetry, J.Zhang, J.S.Taylor, W.Yang, and Z.Suo (2007).
Mechanism of template-independent nucleotide incorporation catalyzed by a template-dependent DNA polymerase.
  J Mol Biol, 365, 590-602.
PDB code: 2imw
17118716 M.E.Arana, K.Takata, M.Garcia-Diaz, R.D.Wood, and T.A.Kunkel (2007).
A unique error signature for human DNA polymerase nu.
  DNA Repair (Amst), 6, 213-223.  
17475573 M.Garcia-Diaz, K.Bebenek, J.M.Krahn, L.C.Pedersen, and T.A.Kunkel (2007).
Role of the catalytic metal during polymerization by DNA polymerase lambda.
  DNA Repair (Amst), 6, 1333-1340.
PDB codes: 2pfn 2pfo 2pfp 2pfq
18496613 M.Garcia-Diaz, and K.Bebenek (2007).
Multiple functions of DNA polymerases.
  CRC Crit Rev Plant Sci, 26, 105-122.  
17947582 N.C.Brissett, R.S.Pitcher, R.Juarez, A.J.Picher, A.J.Green, T.R.Dafforn, G.C.Fox, L.Blanco, and A.J.Doherty (2007).
Structure of a NHEJ polymerase-mediated DNA synaptic complex.
  Science, 318, 456-459.
PDB code: 2r9l
17400246 P.R.Meyer, W.Rutvisuttinunt, S.E.Matsuura, A.G.So, and W.A.Scott (2007).
Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet.
  J Mol Biol, 369, 41-54.  
17303570 V.J.Cannistraro, and J.S.Taylor (2007).
Ability of polymerase eta and T7 DNA polymerase to bypass bulge structures.
  J Biol Chem, 282, 11188-11196.  
16807316 A.J.Picher, M.García-Díaz, K.Bebenek, L.C.Pedersen, T.A.Kunkel, and L.Blanco (2006).
Promiscuous mismatch extension by human DNA polymerase lambda.
  Nucleic Acids Res, 34, 3259-3266.
PDB code: 2gws
16860755 B.Bertocci, A.De Smet, J.C.Weill, and C.A.Reynaud (2006).
Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo.
  Immunity, 25, 31-41.  
17052459 E.Kashkina, M.Anikin, F.Brueckner, R.T.Pomerantz, W.T.McAllister, P.Cramer, and D.Temiakov (2006).
Template misalignment in multisubunit RNA polymerases and transcription fidelity.
  Mol Cell, 24, 257-266.  
16545956 M.Garcia-Diaz, and T.A.Kunkel (2006).
Mechanism of a genetic glissando: structural biology of indel mutations.
  Trends Biochem Sci, 31, 206-214.  
17052458 R.T.Pomerantz, D.Temiakov, M.Anikin, D.G.Vassylyev, and W.T.McAllister (2006).
A mechanism of nucleotide misincorporation during transcription due to template-strand misalignment.
  Mol Cell, 24, 245-255.  
17005572 W.W.Duym, K.A.Fiala, N.Bhatt, and Z.Suo (2006).
Kinetic effect of a downstream strand and its 5'-terminal moieties on single nucleotide gap-filling synthesis catalyzed by human DNA polymerase lambda.
  J Biol Chem, 281, 35649-35655.  
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.