6P1N

Pre-catalytic ternary complex of human DNA Polymerase Mu with 1-nt gapped substrate containing template 8OG and bound incoming dAMPNPP

6P1N の概要

• エントリーDOI: 10.2210/pdb6p1n/pdb
• 分子名称: DNA-directed DNA/RNA polymerase mu, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, DNA (5'-D(*CP*GP*GP*CP*(8OG)P*TP*AP*CP*G)-3'), ... (11 entities in total)
• 機能のキーワード: family x polymerase, nhej, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 45994.76

構造登録者

Kaminski, A.M.,Pedersen, L.C.,Bebenek, K.,Chiruvella, K.K.,Ramsden, D.A.,Kunkel, T.A. (登録日: 2019-05-20, 公開日: 2019-09-04, 最終更新日: 2023-10-11)

主引用文献

Kaminski, A.M.,Chiruvella, K.K.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C.
Unexpected behavior of DNA polymerase Mu opposite template 8-oxo-7,8-dihydro-2'-guanosine.
Nucleic Acids Res., 47:9410-9422, 2019

PubMed Abstract: DNA double-strand breaks (DSBs) resulting from reactive oxygen species generated by exposure to UV and ionizing radiation are characterized by clusters of lesions near break sites. Such complex DSBs are repaired slowly, and their persistence can have severe consequences for human health. We have therefore probed DNA break repair containing a template 8-oxo-7,8-dihydro-2'-guanosine (8OG) by Family X Polymerase μ (Pol μ) in steady-state kinetics and cell-based assays. Pol μ tolerates 8OG-containing template DNA substrates, and the filled products can be subsequently ligated by DNA Ligase IV during Nonhomologous end-joining. Furthermore, Pol μ exhibits a strong preference for mutagenic bypass of 8OG by insertion of adenine. Crystal structures reveal that the template 8OG is accommodated in the Pol μ active site with none of the DNA substrate distortions observed for Family X siblings Pols β or λ. Kinetic characterization of template 8OG bypass indicates that Pol μ inserts adenosine nucleotides with weak sugar selectivity and, given the high cellular concentration of ATP, likely performs its role in repair of complex 8OG-containing DSBs using ribonucleotides.

PubMed: 31435651
DOI: 10.1093/nar/gkz680

実験手法

X-RAY DIFFRACTION (1.6 Å)