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PDBsum entry 2bcs
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Transferase, lyase/DNA
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PDB id
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2bcs
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References listed in PDB file
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Key reference
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Title
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Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase.
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Authors
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M.Garcia-Diaz,
K.Bebenek,
J.M.Krahn,
L.C.Pedersen,
T.A.Kunkel.
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Ref.
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Cell, 2006,
124,
331-342.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 3.
Figure 3. The Extrahelical Adenine Is in Close Proximity to
β strand 8
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Figure 4.
Figure 4. Pol λ Can Tolerate Distortion upstream of the
Primer Terminus
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2006,
124,
331-342)
copyright 2006.
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