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PDBsum entry 3g6x
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Replication/DNA
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PDB id
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3g6x
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References listed in PDB file
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Key reference
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Title
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Dna synthesis across an abasic lesion by human DNA polymerase iota.
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Authors
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D.T.Nair,
R.E.Johnson,
L.Prakash,
S.Prakash,
A.K.Aggarwal.
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Ref.
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Structure, 2009,
17,
530-537.
[DOI no: ]
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PubMed id
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Abstract
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Abasic sites are among the most abundant DNA lesions formed in human cells, and
they present a strong block to replication. DNA polymerase iota (Poliota) is one
of the few DNA Pols that does not follow the A-rule opposite an abasic site. We
present here three structures of human Poliota in complex with DNAs containing
an abasic lesion and dGTP, dTTP, or dATP as the incoming nucleotide. The
structures reveal a mechanism of translesion synthesis across an abasic lesion
that differs from that in other Pols. Both the abasic lesion and the incoming
dNTPs are intrahelical and are closely apposed across a constricted active site
cleft. The dNTPs partake in distinct networks of hydrogen bonds in the "void"
opposite the lesion. These different patterns of hydrogen bonds, as well as
stacking interactions, may underlie Poliota's small preference for insertion of
dGTP over other nucleotides opposite this common lesion.
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Figure 3.
Figure 3. Hydrogen-Bonding Networks
(A) Hydrogen bonding
between the dGTP base and polymerase in the Polι[Abasic.dGTP]
ternary complex. The relevant DNA and protein residues are
colored according to element, the water molecules are shown as
red spheres, and the hydrogen bonds are displayed as dashed
lines.
(B) Hydrogen bonding between the dTTP base and
polymerase in the Polι[Abasic.dTTP] ternary complex.
(C)
Hydrogen bonding between the dATP base and polymerase in the
Polι[Abasic.dATP] ternary complex.
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Figure 4.
Figure 4. Comparison of Dpo4[Abasic.dCTP] and
Polι[Abasic.dTTP] Ternary Complexes
The protein surface is
displayed in light blue (Dpo4) or cyan (Polι), DNA is shown in
stick representation, and putative Mg^2+ (Polι) or Ca^2+ (Dpo4)
ions are shown as dark blue spheres. The abasic site and the
incoming dTTP (Polι) or dCTP (Dpo4) are colored in red. The
nucleotide 5′ to the abasic site in the Dpo4 complex is
colored in sky blue. The abasic site is extrahelical in the Dpo4
complex (Ling et al., 2004), but remains intrahelical in the
Polι complex(es).
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2009,
17,
530-537)
copyright 2009.
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