Summary information and primary citation
- PDB-id
- 7ktl; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- replication
- Method
- X-ray (1.421 Å)
- Summary
- DNA polymerase mu (k438d), 8-oxodgtp:ct product state ternary complex, 50 mm mn2+ (90min)
- Reference
- Jamsen JA, Sassa A, Shock DD, Beard WA, Wilson SH (2021): "Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide." Nat Commun, 12, 2059. doi: 10.1038/s41467-021-21354-6.
- Abstract
- Oxidized dGTP (8-oxo-7,8-dihydro-2´-deoxyguanosine triphosphate, 8-oxodGTP) insertion by DNA polymerases strongly promotes cancer and human disease. How DNA polymerases discriminate against oxidized and undamaged nucleotides, especially in error-prone double strand break (DSB) repair, is poorly understood. High-resolution time-lapse X-ray crystallography snapshots of DSB repair polymerase μ undergoing DNA synthesis reveal that a third active site metal promotes insertion of oxidized and undamaged dGTP in the canonical anti-conformation opposite template cytosine. The product metal bridged O8 with product oxygens, and was not observed in the syn-conformation opposite template adenine (At). Rotation of At into the syn-conformation enabled undamaged dGTP misinsertion. Exploiting metal and substrate dynamics in a rigid active site allows 8-oxodGTP to circumvent polymerase fidelity safeguards to promote pro-mutagenic double strand break repair.
