Summary information and primary citation
- PDB-id
-
6btf;
SNAP-derived features in text and
JSON formats
- Class
- transferase,lyase-DNA
- Method
- X-ray (1.75 Å)
- Summary
- DNA polymerase beta i260q ternary complex
- Reference
-
Liptak C, Mahmoud MM, Eckenroth BE, Moreno MV, East K,
Alnajjar KS, Huang J, Towle-Weicksel JB, Doublie S, Loria
JP, Sweasy JB (2018): "I260Q DNA
polymerase beta highlights precatalytic conformational
rearrangements critical for fidelity." Nucleic
Acids Res., 46, 10740-10756. doi:
10.1093/nar/gky825.
- Abstract
- DNA polymerase β (pol β) fills single nucleotide gaps
in DNA during base excision repair and non-homologous
end-joining. Pol β must select the correct nucleotide from
among a pool of four nucleotides with similar structures
and properties in order to maintain genomic stability
during DNA repair. Here, we use a combination of X-ray
crystallography, fluorescence resonance energy transfer and
nuclear magnetic resonance to show that pol β's ability to
access the appropriate conformations both before and upon
binding to nucleotide substrates is integral to its
fidelity. Importantly, we also demonstrate that the
inability of the I260Q mutator variant of pol β to properly
navigate this conformational landscape results in
error-prone DNA synthesis. Our work reveals that
precatalytic conformational rearrangements themselves are
an important underlying mechanism of substrate selection by
DNA pol β.
