ArticleNucleic acids research2014
Requirements for 5'dRP/AP lyase activity in Ku.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Amphiphilic Oligonucleotide Derivatives as a Tool to Study DNA Repair Proteins.International journal of molecular sciences · 2025Article
- Self-Penetrating Oligonucleotide Derivatives: Features of Self-Assembly and Interactions with Serum and Intracellular Proteins.Pharmaceutics · 2023Article
- Reconsidering the Chemical Nature of Strand Breaks Derived from Abasic Sites in Cellular DNA: Evidence for 3'-Glutathionylation.Journal of the American Chemical Society · 2022Article
- Unexpected Complexity in the Products Arising from NaOH-, Heat-, Amine-, and Glycosylase-Induced Strand Cleavage at an Abasic Site in DNA.Chemical research in toxicology · 2022Article
- Products Generated by Amine-Catalyzed Strand Cleavage at Apurinic/Apyrimidinic Sites in DNA: New Insights from a Biomimetic Nucleoside Model System.Chemical research in toxicology · 2022Article
- Oxidative DNA-protein crosslinks formed in mammalian cells by abasic site lyases involved in DNA repair.DNA repair · 2020Article
- Bacterial Ligase D preternary-precatalytic complex performs efficient abasic sites processing at double strand breaks during nonhomologous end joining.Nucleic acids research · 2019Article
- Expanded Substrate Scope of DNA Polymerase θ and DNA Polymerase β: Lyase Activity on 5'-Overhangs and Clustered Lesions.Biochemistry · 2018Article
- Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA.Nucleic acids research · 2017Article
- Cloning, localization and focus formation at DNA damage sites of canine Ku70.The Journal of veterinary medical science · 2017Article
- When DNA repair goes wrong: BER-generated DNA-protein crosslinks to oxidative lesions.DNA repair · 2016Review
- Overhang polarity of chromosomal double-strand breaks impacts kinetics and fidelity of yeast non-homologous end joining.Nucleic acids research · 2016Article
- Identification of a conserved 5'-dRP lyase activity in bacterial DNA repair ligase D and its potential role in base excision repair.Nucleic acids research · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The non-homologous end joining (NHEJ) pathway is used in diverse species to repair chromosome breaks, and is defined in part by a requirement for Ku. We previously demonstrated mammalian Ku has intrinsic 5' deoxyribosephosphate (5'dRP) and apurinic/apyrimidinic (AP) lyase activity, and showed this activity is important for excising abasic site damage from ends. Here we employ systematic mutagenesis to clarify the protein requirements for this activity. We identify lysine 31 in the 70 kD subunit (Ku70 K31) as the primary candidate nucleophile required for catalysis, but additional mutation of Ku70 K160 and six other lysines within Ku80 were required to eliminate all activity. Ku from Saccharomyces cerevisiae also possesses 5'dRP/AP lyase activity, and robust activity was also reliant on lysines in Ku70 analogous to K31 and K160. By comparison, these lysines are not conserved in Xenopus laevis Ku, and Ku from this species has negligible activity. A role for residues flanking Ku70 K31 in expanding the range of abasic site contexts that can be used as substrate was also identified. Our results suggest an active site well located to provide the substrate specificity required for its biological role.
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