7COA

Ternary complex of DNA polymerase Mu with 1-nt gapped DNA (T:dGMPNPP) and Mn

Summary for 7COA

• Entry DOI: 10.2210/pdb7coa/pdb
• Descriptor: DNA-directed DNA/RNA polymerase mu, DNA (5'-D(*CP*GP*GP*CP*TP*TP*AP*CP*G)-3'), DNA (5'-D(*CP*GP*TP*A)-3'), ... (8 entities in total)
• Functional Keywords: polymerase mu, misincorporation, gap filling, mutagenesis, hydrolase, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 59565.78

Authors

Guo, M.,Zhao, Y. (deposition date: 2020-08-04, release date: 2021-06-30, Last modification date: 2023-11-29)

Primary citation

Guo, M.,Wang, Y.,Tang, Y.,Chen, Z.,Hou, J.,Dai, J.,Wang, Y.,Wang, L.,Xu, H.,Tian, B.,Hua, Y.,Zhao, Y.
Mechanism of genome instability mediated by human DNA polymerase mu misincorporation.
Nat Commun, 12:3759-3759, 2021

PubMed Abstract: Pol μ is capable of performing gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Together with DNA ligase, misincorporation of dGTP opposite the templating T by Pol μ results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinetics of Pol μ substituting dGTP for dATP on gapped DNA substrates containing templating T were determined and compared. Pol μ is highly mutagenic on a 2-nt gapped DNA substrate, with T:dGTP base pairing at the 3' end of the gap. Two residues (Lys438 and Gln441) interact with T:dGTP and fine tune the active site microenvironments. The in-crystal misincorporation reaction of Pol μ revealed an unexpected second dGTP in the active site, suggesting its potential mutagenic role among human X family polymerases in NHEJ.

PubMed: 34145298
DOI: 10.1038/s41467-021-24096-7

Experimental method

X-RAY DIFFRACTION (1.698 Å)