2BCS: Dna Polymerase Lambda In Complex With A Dna Duplex Containing An Unpaired Dcmp

Citation:
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.
PDB ID: 2BCSDownload
MMDB ID: 86783
PDB Deposition Date: 2005/10/19
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2BCS: tetrameric; determined by author
Molecular Components in 2BCS
Label Count Molecule
Protein (1 molecule)
1
DNA Polymerase Lambda(Gene symbol: POLL)
Molecule annotation
Nucleotides(3 molecules)
1
5'-d(*gp*cp*cp*g)-3'
Molecule annotation
1
5'-d(*cp*ap*gp*tp*ap*cp*g)-3'
Molecule annotation
1
5'-d(*cp*gp*gp*cp*cp*gp*cp*tp*ap*cp*tp*g)-3'
Molecule annotation
Chemicals (4 molecules)
1
1
2
2
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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