7KR4

Human DNA Ligase 1(E346A/E592A) Bound to a nicked DNA substrate control duplex

7KR4 の概要

• エントリーDOI: 10.2210/pdb7kr4/pdb
• 分子名称: DNA ligase 1, DNA (5'-D(*AP*AP*TP*GP*TP*CP*TP*GP*CP*CP*C)-3'), DNA (5'-D(P*AP*TP*TP*CP*TP*GP*C)-3'), ... (7 entities in total)
• 機能のキーワード: dna ligase, dna replication, dna repair, replication fidelity, ligase, ligase-dna complex, ligase/dna
• 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: 83486.84

構造登録者

Tumbale, P.P.,Williams, R.S. (登録日: 2020-11-18, 公開日: 2021-02-03, 最終更新日: 2023-10-18)

主引用文献

Williams, J.S.,Tumbale, P.P.,Arana, M.E.,Rana, J.A.,Williams, R.S.,Kunkel, T.A.
High-fidelity DNA ligation enforces accurate Okazaki fragment maturation during DNA replication.
Nat Commun, 12:482-482, 2021

PubMed Abstract: DNA ligase 1 (LIG1, Cdc9 in yeast) finalizes eukaryotic nuclear DNA replication by sealing Okazaki fragments using DNA end-joining reactions that strongly discriminate against incorrectly paired DNA substrates. Whether intrinsic ligation fidelity contributes to the accuracy of replication of the nuclear genome is unknown. Here, we show that an engineered low-fidelity LIG1 variant confers a novel mutator phenotype in yeast typified by the accumulation of single base insertion mutations in homonucleotide runs. The rate at which these additions are generated increases upon concomitant inactivation of DNA mismatch repair, or by inactivation of the Fen1 Okazaki fragment maturation (OFM) nuclease. Biochemical and structural data establish that LIG1 normally avoids erroneous ligation of DNA polymerase slippage products, and this protection is compromised by mutation of a LIG1 high-fidelity metal binding site. Collectively, our data indicate that high-fidelity DNA ligation is required to prevent insertion mutations, and that this may be particularly critical following strand displacement synthesis during the completion of OFM.

PubMed: 33473124
DOI: 10.1038/s41467-020-20800-1

実験手法

X-RAY DIFFRACTION (2.2 Å)