6P0E

Human DNA Ligase 1 (E346A,E592A) bound to adenylated DNA containing an 8-oxo guanine:adenine base-pair

Summary for 6P0E

• Entry DOI: 10.2210/pdb6p0e/pdb
• Descriptor: DNA ligase 1, DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*TP*(8OG))-3'), DNA (5'-D(P*GP*TP*CP*GP*GP*AP*C)-3'), ... (8 entities in total)
• Functional Keywords: protein-dna complex, phosphotransferase, ob fold, dna binding domain, adenylation domain, metalloenzyme, ligase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 83397.77

Authors

Schellenberg, M.J.,Williams, R.S.,Tumbale, P.S.,Riccio, A.A. (deposition date: 2019-05-16, release date: 2019-12-11, Last modification date: 2023-10-11)

Primary citation

Tumbale, P.P.,Jurkiw, T.J.,Schellenberg, M.J.,Riccio, A.A.,O'Brien, P.J.,Williams, R.S.
Two-tiered enforcement of high-fidelity DNA ligation.
Nat Commun, 10:5431-5431, 2019

PubMed Abstract: DNA ligases catalyze the joining of DNA strands to complete DNA replication, recombination and repair transactions. To protect the integrity of the genome, DNA ligase 1 (LIG1) discriminates against DNA junctions harboring mutagenic 3'-DNA mismatches or oxidative DNA damage, but how such high-fidelity ligation is enforced is unknown. Here, X-ray structures and kinetic analyses of LIG1 complexes with undamaged and oxidatively damaged DNA unveil that LIG1 employs Mg-reinforced DNA binding to validate DNA base pairing during the adenylyl transfer and nick-sealing ligation reaction steps. Our results support a model whereby LIG1 fidelity is governed by a high-fidelity (HiFi) interface between LIG1, Mg, and the DNA substrate that tunes the enzyme to release pro-mutagenic DNA nicks. In a second tier of protection, LIG1 activity is surveilled by Aprataxin (APTX), which suppresses mutagenic and abortive ligation at sites of oxidative DNA damage.

PubMed: 31780661
DOI: 10.1038/s41467-019-13478-7

Experimental method

X-RAY DIFFRACTION (1.85 Å)