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PDBsum entry 5iio
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Transferase/DNA
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PDB id
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5iio
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PDB id:
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Transferase/DNA
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Title:
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Crystal structure of the DNA polymerase lambda binary complex
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Structure:
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DNA (5'-d( Cp Gp Gp Cp (8Og)p Gp Tp Ap Cp Tp G)-3'). Chain: b, f, j, n. Engineered: yes. DNA (5'-d( Cp Ap Gp Tp Ap C)-3'). Chain: c, g, k, o. Engineered: yes. DNA (5'-d(p Gp Cp Cp G)-3'). Chain: d, h, l, p. Engineered: yes.
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Source:
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Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Homo sapiens. Human. Organism_taxid: 9606. Gene: poll. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.08Å
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R-factor:
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0.192
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R-free:
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0.235
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Authors:
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M.J.Burak,K.E.Guja,M.Garcia-Diaz
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Key ref:
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M.J.Burak
et al.
(2016).
A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG.
Embo J,
35,
2045-2059.
PubMed id:
DOI:
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Date:
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01-Mar-16
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Release date:
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17-Aug-16
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PROCHECK
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Headers
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References
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Q9UGP5
(DPOLL_HUMAN) -
DNA polymerase lambda from Homo sapiens
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Seq:
Struc:
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575 a.a.
327 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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C-G-G-C-8OG-G-T-A-C-T-G
11 bases
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C-A-G-T-A-C
6 bases
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G-C-C-G
4 bases
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C-G-G-C-8OG-G-T-A-C-T-G
11 bases
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C-A-G-T-A-C
6 bases
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G-C-C-G
4 bases
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C-G-G-C-8OG-G-T-A-C-T-G
11 bases
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C-A-G-T-A-C
6 bases
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G-C-C-G
4 bases
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C-G-G-C-8OG-G-T-A-C-T-G
11 bases
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C-A-G-T-A-C
6 bases
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G-C-C-G
4 bases
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Enzyme class 2:
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E.C.2.7.7.7
- DNA-directed Dna polymerase.
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Reaction:
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DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
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DNA(n)
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+
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2'-deoxyribonucleoside 5'-triphosphate
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=
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DNA(n+1)
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+
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diphosphate
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Enzyme class 3:
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E.C.4.2.99.-
- ?????
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Embo J
35:2045-2059
(2016)
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PubMed id:
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A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG.
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M.J.Burak,
K.E.Guja,
E.Hambardjieva,
B.Derkunt,
M.Garcia-Diaz.
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ABSTRACT
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8-oxo-7,8-dihydroxy-2'-deoxyguanosine (8-oxo-dG) has high mutagenic potential as
it is prone to mispair with deoxyadenine (dA). In order to maintain genomic
integrity, post-replicative 8-oxo-dG:dA mispairs are removed through DNA
polymerase lambda (Pol λ)-dependent MUTYH-initiated base excision repair (BER).
Here, we describe seven novel crystal structures and kinetic data that fully
characterize 8-oxo-dG bypass by Pol λ. We demonstrate that Pol λ has a
flexible active site that can tolerate 8-oxo-dG in either the anti- or
syn-conformation. Importantly, we show that discrimination against the
pro-mutagenic syn-conformation occurs at the extension step and identify the
residue responsible for this selectivity. This residue acts as a kinetic switch,
shunting repair toward long-patch BER upon correct dCMP incorporation, thus
enhancing repair efficiency. Moreover, this switch also provides a potential
mechanism to increase repair fidelity of MUTYH-initiated BER.
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