ArticleThe Biochemical journal2013
A covalent protein-DNA 5'-product adduct is generated following AP lyase activity of human ALKBH1 (AlkB homologue 1).
Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- ALKBH1: emerging biomarker and therapeutic target for cancer treatment.Discover oncology · 2024Review
- Unprecedented reactivity of polyamines with aldehydic DNA modifications: structural determinants of reactivity, characterization and enzymatic stability of adducts.Nucleic acids research · 2023Article
- A DNA adenine demethylase impairs PRC2-mediated repression of genes marked by a specific chromatin signature.Genome biology · 2023Article
- Exploring links between 2-oxoglutarate-dependent oxygenases and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Review
- Spectroscopic and in vitro Investigations of FeChembiochem : a European journal of chemical biology · 2022Review
- DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases.International journal of molecular sciences · 2021Review
- Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family.Cellular and molecular life sciences : CMLS · 2021Review
- Reversible RNA Modification NGenomics, proteomics & bioinformatics · 2018Review
- Characterization of human AlkB homolog 1 produced in mammalian cells and demonstration of mitochondrial dysfunction in ALKBH1-deficient cells.Biochemical and biophysical research communications · 2018Article
- Biochemical Characterization of AP Lyase and mBiochemistry · 2017Article
- The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond.The Journal of biological chemistry · 2015Review
- Homology modeling, molecular dynamics, and site-directed mutagenesis study of AlkB human homolog 1 (ALKBH1).Journal of molecular graphics & modelling · 2014Article
- Looking beneath the surface to determine what makes DNA damage deleterious.Current opinion in chemical biology · 2014Review
- Nucleic acid oxidation in DNA damage repair and epigenetics.Chemical reviews · 2014Review
- Abasic and oxidized abasic site reactivity in DNA: enzyme inhibition, cross-linking, and nucleosome catalyzed reactions.Accounts of chemical research · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
ALKBH1 (AlkB homologue 1) is a mammalian AlkB (2-oxoglutarate-dependent dioxygenase) homologue that possesses AP (abasic or apurinic/apyrimidinic) lyase activity. The AP lyase reaction is catalysed by imine formation with an active site lysine residue, and a covalent intermediate can be trapped in the presence of NaBH4. Surprisingly, ALKBH1 also forms a stable protein-DNA adduct in the absence of a reducing agent. Experiments with different substrates demonstrated that the protein covalently binds to the 5' DNA product, i.e. the fragment containing an α,β-unsaturated aldehyde. The N-terminal domain of ALKBH1 was identified as the main site of linkage with DNA. By contrast, mutagenesis studies suggest that the primary catalytic residue forming the imine linkage is Lys133, with Lys154 and other lysine residues in this region serving in opportunistic roles. These findings confirm the classification of ALKBH1 as an AP lyase, identify the primary and a secondary lysine residues involved in the lyase reaction, and demonstrate that the protein forms a covalent adduct with the 5' DNA product. We propose two plausible chemical mechanisms to account for the covalent attachment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.