ArticlebioRxiv : the preprint server for biology2024
Structural and biochemical characterization of LIG1 during mutagenic nick sealing of oxidatively damaged ends at the final step of DNA repair.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
DNA ligase 1 (LIG1) joins broken strand-breaks in the phosphodiester backbone to finalize DNA repair pathways. We previously reported that LIG1 fails on nick repair intermediate with 3'-oxidative damage incorporated by DNA polymerase (pol) β at the downstream steps of base excision repair (BER) pathway. Here, we determined X-ray structures of LIG1/nick DNA complexes containing 3'-8oxodG and 3'-8oxorG opposite either a templating Cytosine or Adenine and demonstrated that the ligase active site engages with mutagenic repair intermediates during steps 2 and 3 of the ligation reaction referring to the formation of DNA-AMP intermediate and a final phosphodiester bond, respectively. Furthermore, we showed the mutagenic nick sealing of DNA substrates with 3'-8oxodG:A and 3'-8oxorG:A by LIG1 wild-type, immunodeficiency disease-associated variants, and DNA ligase 3α (LIG3α)
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