Summary information and primary citation
- PDB-id
-
5iim;
DSSR-derived features in text and
JSON formats
- Class
- transferase-DNA
- Method
- X-ray (1.941 Å)
- Summary
- Crystal structure of the pre-catalytic ternary
extension complex of DNA polymerase lambda with an
8-oxo-dg:da base-pair
- Reference
-
Burak MJ, Guja KE, Hambardjieva E, Derkunt B, Garcia-Diaz
M (2016): "A fidelity
mechanism in DNA polymerase lambda promotes error-free
bypass of 8-oxo-dG." Embo J.,
35, 2045-2059. doi: 10.15252/embj.201694332.
- Abstract
- 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.
