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PDBsum entry 4rpy
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Transferase/DNA
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PDB id
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4rpy
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References listed in PDB file
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Key reference
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Title
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Viewing human DNA polymerase β faithfully and unfaithfully bypass an oxidative lesion by time-Dependent crystallography.
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Authors
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R.Vyas,
A.J.Reed,
E.J.Tokarsky,
Z.Suo.
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Ref.
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J Am Chem Soc, 2015,
137,
5225-5230.
[DOI no: ]
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PubMed id
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Abstract
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One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), is
highly mutagenic in vivo due to its anti-conformation forming a Watson-Crick
base pair with correct deoxycytidine 5'-triphosphate (dCTP) and its
syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine
5'-triphosphate (dATP). Here, we utilized time-resolved X-ray crystallography to
follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved
structures, both Watson-Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen
(syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained
throughout the chemical reaction. Additionally, a third Mg(2+) appeared during
the process of phosphodiester bond formation and was located between the
reacting α- and β-phosphates of the dNTP, suggesting its role in stabilizing
reaction intermediates. After phosphodiester bond formation, hPolβ reopened its
conformation, pyrophosphate was released, and the newly incorporated primer
3'-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These
structures provide the first real-time pictures, to our knowledge, of how a
polymerase correctly and incorrectly bypasses a DNA lesion.
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