Summary information and primary citation

PDB-id
7coc; SNAP-derived features in text and JSON formats; DNAproDB
Class
hydrolase-DNA
Method
X-ray (1.9 Å)
Summary
Ternary complex of DNA polymerase mu (k438a-q441a) with 1-nt gapped DNA (t:dgmpnpp)
Reference
Guo M, Wang Y, Tang Y, Chen Z, Hou J, Dai J, Wang Y, Wang L, Xu H, Tian B, Hua Y, Zhao Y (2021): "Mechanism of genome instability mediated by human DNA polymerase mu misincorporation." Nat Commun, 12, 3759. doi: 10.1038/s41467-021-24096-7.
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.

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