Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

7KSV

DNA Polymerase Mu, dGTP:Ct Product State Ternary Complex, 10 mM Mn2+ (960min)

Summary for 7KSV
Entry DOI10.2210/pdb7ksv/pdb
DescriptorDNA-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 Keywordstime-lapse crystallography, oxidized nucleotide insertion, dna polymerase mu, double strand break repair, replication, replication-dna complex, replication/dna
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains4
Total formula weight46830.96
Authors
Jamsen, J.A.,Wilson, S.H. (deposition date: 2020-11-24, release date: 2021-12-01, Last modification date: 2023-11-15)
Primary citationJamsen, 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: 33824325
DOI: 10.1038/s41467-021-21354-6
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.64 Å)
Structure validation

227561

PDB entries from 2024-11-20

PDB statisticsPDBj update infoContact PDBjnumon