7KSV
DNA Polymerase Mu, dGTP:Ct Product State Ternary Complex, 10 mM Mn2+ (960min)
Summary for 7KSV
Entry DOI | 10.2210/pdb7ksv/pdb |
Descriptor | DNA-directed DNA/RNA polymerase mu, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, DNA (5'-D(*CP*GP*GP*CP*CP*TP*AP*CP*G)-3'), ... (11 entities in total) |
Functional Keywords | time-lapse crystallography, oxidized nucleotide insertion, dna polymerase mu, double strand break repair, replication, replication-dna complex, replication/dna |
Biological source | Homo sapiens (Human) More |
Total number of polymer chains | 4 |
Total formula weight | 46830.96 |
Authors | Jamsen, J.A.,Wilson, S.H. (deposition date: 2020-11-24, release date: 2021-12-01, Last modification date: 2023-11-15) |
Primary citation | Jamsen, J.A.,Sassa, A.,Shock, D.D.,Beard, W.A.,Wilson, S.H. Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide. Nat Commun, 12:2059-2059, 2021 Cited by PubMed 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 (A). Rotation of A 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. PubMed: 33824325DOI: 10.1038/s41467-021-21354-6 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.64 Å) |
Structure validation
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