 |
PDBsum entry 3in5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/DNA
|
PDB id
|
|
|
|
3in5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of human DNA polymerase kappa inserting datp opposite an 8-Oxog DNA lesion.
|
|
|
Authors
|
|
R.Vasquez-Del carpio,
T.D.Silverstein,
S.Lone,
M.K.Swan,
J.R.Choudhury,
R.E.Johnson,
S.Prakash,
L.Prakash,
A.K.Aggarwal.
|
|
|
Ref.
|
|
Plos One, 2009,
4,
e5766.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
BACKGROUND: Oxygen-free radicals formed during normal aerobic cellular
metabolism attack bases in DNA and 7,8-dihydro-8-oxoguanine (8-oxoG) is one of
the major lesions formed. It is amongst the most mutagenic lesions in cells
because of its dual coding potential, wherein 8-oxoG(syn) can pair with an A in
addition to normal base pairing of 8-oxoG(anti) with a C. Human DNA polymerase
kappa (Polkappa) is a member of the newly discovered Y-family of DNA polymerases
that possess the ability to replicate through DNA lesions. To understand the
basis of Polkappa's preference for insertion of an A opposite 8-oxoG lesion, we
have solved the structure of Polkappa in ternary complex with a template-primer
presenting 8-oxoG in the active site and with dATP as the incoming nucleotide.
METHODOLOGY AND PRINCIPAL FINDINGS: We show that the Polkappa active site is
well-adapted to accommodate 8-oxoG in the syn conformation. That is, the
polymerase and the bound template-primer are almost identical in their
conformations to that in the ternary complex with undamaged DNA. There is no
steric hindrance to accommodating 8-oxoG in the syn conformation for Hoogsteen
base-paring with incoming dATP. CONCLUSIONS AND SIGNIFICANCE: The structure we
present here is the first for a eukaryotic translesion synthesis (TLS) DNA
polymerase with an 8-oxoG:A base pair in the active site. The structure shows
why Polkappa is more efficient at inserting an A opposite the 8-oxoG lesion than
a C. The structure also provides a basis for why Polkappa is more efficient at
inserting an A opposite the lesion than other Y-family DNA polymerases.
|
|
|
|
|
|
|
