2bcv
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DNA polymerase lambda in complex with Dttp and a DNA duplex containing an unpaired Dtmp
OverviewOverview
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.
About this StructureAbout this Structure
2BCV is a Single protein structure of sequence from Homo sapiens with MG, NA and TTP as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase., Garcia-Diaz M, Bebenek K, Krahn JM, Pedersen LC, Kunkel TA, Cell. 2006 Jan 27;124(2):331-42. PMID:16439207
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