2bcq

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Revision as of 18:54, 12 November 2007

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spinqualitylabelsall models 2bcq, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

DNA polymerase lambda in complex with a DNA duplex containing an unpaired Dtmp

Overview

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 Structure

2BCQ is a Single protein structure of sequence from Homo sapiens with NA, MG, PPV and EDO as ligands. Full crystallographic information is available from OCA.

Reference

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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