6WID

Nucleotide incorporation intermediate into quaternary complex of human Polymerase Mu on a complementary DNA double-strand break substrate

6WID の概要

• エントリーDOI: 10.2210/pdb6wid/pdb
• 分子名称: DNA-directed DNA/RNA polymerase mu, CHLORIDE ION, PENTAETHYLENE GLYCOL, ... (14 entities in total)
• 機能のキーワード: family x polymerase, nonhomologous end-joining, dna double-strand break repair, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 46717.90

構造登録者

Kaminski, A.M.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, K. (登録日: 2020-04-09, 公開日: 2020-10-07, 最終更新日: 2023-10-18)

主引用文献

Kaminski, A.M.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Pedersen, L.C.,Bebenek, K.
Structural snapshots of human DNA polymerase mu engaged on a DNA double-strand break.
Nat Commun, 11:4784-4784, 2020

PubMed Abstract: Genomic integrity is threatened by cytotoxic DNA double-strand breaks (DSBs), which must be resolved efficiently to prevent sequence loss, chromosomal rearrangements/translocations, or cell death. Polymerase μ (Polμ) participates in DSB repair via the nonhomologous end-joining (NHEJ) pathway, by filling small sequence gaps in broken ends to create substrates ultimately ligatable by DNA Ligase IV. Here we present structures of human Polμ engaging a DSB substrate. Synapsis is mediated solely by Polμ, facilitated by single-nucleotide homology at the break site, wherein both ends of the discontinuous template strand are stabilized by a hydrogen bonding network. The active site in the quaternary Pol μ complex is poised for catalysis and nucleotide incoporation proceeds in crystallo. These structures demonstrate that Polμ may address complementary DSB substrates during NHEJ in a manner indistinguishable from single-strand breaks.

PubMed: 32963245
DOI: 10.1038/s41467-020-18506-5

実験手法

X-RAY DIFFRACTION (1.5 Å)