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PDBsum entry 3lwl
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Transferase/DNA
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PDB id
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3lwl
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References listed in PDB file
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Key reference
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Title
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Replication through an abasic DNA lesion: structural basis for adenine selectivity.
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Authors
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S.Obeid,
N.Blatter,
R.Kranaster,
A.Schnur,
K.Diederichs,
W.Welte,
A.Marx.
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Ref.
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Embo J, 2010,
29,
1738-1747.
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PubMed id
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Abstract
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Abasic sites represent the most frequent DNA lesions in the genome that have
high mutagenic potential and lead to mutations commonly found in human cancers.
Although these lesions are devoid of the genetic information, adenine is most
efficiently inserted when abasic sites are bypassed by DNA polymerases, a
phenomenon termed A-rule. In this study, we present X-ray structures of a DNA
polymerase caught while incorporating a nucleotide opposite an abasic site. We
found that a functionally important tyrosine side chain directs for nucleotide
incorporation rather than DNA. It fills the vacant space of the absent template
nucleobase and thereby mimics a pyrimidine nucleobase directing for preferential
purine incorporation opposite abasic residues because of enhanced geometric fit
to the active site. This amino acid templating mechanism was corroborated by
switching to pyrimidine specificity because of mutation of the templating
tyrosine into tryptophan. The tyrosine is located in motif B and highly
conserved throughout evolution from bacteria to humans indicating a general
amino acid templating mechanism for bypass of non-instructive lesions by DNA
polymerases at least from this sequence family.
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