7cob
Ternary complex of DNA polymerase Mu (Q441A) with 1-nt gapped DNA (T:dGMPNPP)
Structural highlights
FunctionDPOLM_HUMAN Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.[1] [2] [3] [4] Publication Abstract from PubMedPol mu 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 mu results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinetics of Pol mu substituting dGTP for dATP on gapped DNA substrates containing templating T were determined and compared. Pol mu 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 mu revealed an unexpected second dGTP in the active site, suggesting its potential mutagenic role among human X family polymerases in NHEJ. Mechanism of genome instability mediated by human DNA polymerase mu misincorporation.,Guo M, Wang Y, Tang Y, Chen Z, Hou J, Dai J, Wang Y, Wang L, Xu H, Tian B, Hua Y, Zhao Y Nat Commun. 2021 Jun 18;12(1):3759. doi: 10.1038/s41467-021-24096-7. PMID:34145298[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
