Summary information and primary citation
- PDB-id
-
7m4e;
SNAP-derived features in text and
JSON formats
- Class
- replication
- Method
- X-ray (1.903 Å)
- Summary
- DNA polymerase lambda, dctp:at mg2+ reaction state
ternary complex, 120 min
- Reference
-
Jamsen JA, Shock DD, Wilson SH (2022): "Watching
right and wrong nucleotide insertion captures hidden
polymerase fidelity checkpoints." Nat
Commun, 13, 3193. doi: 10.1038/s41467-022-30141-w.
- Abstract
- Efficient and accurate DNA synthesis is enabled by DNA
polymerase fidelity checkpoints that promote insertion of
the right instead of wrong nucleotide. Erroneous X-family
polymerase (pol) λ nucleotide insertion leads to genomic
instability in double strand break and base-excision
repair. Here, time-lapse crystallography captures
intermediate catalytic states of pol λ undergoing right and
wrong natural nucleotide insertion. The
revealed nucleotide sensing mechanism responds to base
pair geometry through active site deformation to regulate
global polymerase-substrate complex alignment in support of
distinct optimal (right) or suboptimal (wrong) reaction
pathways. An induced fit during wrong but not right
insertion, and associated metal, substrate, side chain and
pyrophosphate reaction dynamics modulated nucleotide
insertion. A third active site metal hastened right but not
wrong insertion and was not essential for DNA synthesis.
The previously hidden fidelity checkpoints uncovered reveal
fundamental strategies of polymerase DNA repair synthesis
in genomic instability.
