ArticleProceedings of the National Academy of Sciences of the United States of America2000
Catalysis of DNA cleavage and nucleoside triphosphate synthesis by NM23-H2/NDP kinase share an active site that implies a DNA repair function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 93 citations in OpenAlex.
- Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024Review
- NDK/NME proteins: a host-pathogen interface perspective towards therapeutics.Current genetics · 2022Review
- Mechanisms of damage tolerance and repair during DNA replication.Nucleic acids research · 2021Review
- Diverse roles of nucleoside diphosphate kinase in genome stability and growth fitness.Current genetics · 2020Review
- HMCES safeguards replication from oxidative stress and ensures error-free repair.EMBO reports · 2020Article
- The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage.International journal of molecular sciences · 2020Article
- Arylfluorosulfate-Based Electrophiles for Covalent Protein Labeling: A New Addition to the Arsenal.Angewandte Chemie (International ed. in English) · 2019Review
- "Inverse Drug Discovery" Strategy To Identify Proteins That Are Targeted by Latent Electrophiles As Exemplified by Aryl Fluorosulfates.Journal of the American Chemical Society · 2018Article
- Discovery of novel inhibitors for Leishmania nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization.Journal of computer-aided molecular design · 2017Article
- Biochemical Characterization of AP Lyase and mBiochemistry · 2017Article
- Regulatory functions of Nm23-H2 in tumorigenesis: insights from biochemical to clinical perspectives.Naunyn-Schmiedeberg's archives of pharmacology · 2015Review
- A covalent protein-DNA 5'-product adduct is generated following AP lyase activity of human ALKBH1 (AlkB homologue 1).The Biochemical journal · 2013Article
- Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma.Experimental & molecular medicine · 2012Article
- Metastasis suppressor NM23-H1 promotes repair of UV-induced DNA damage and suppresses UV-induced melanomagenesis.Cancer research · 2012Article
- A critical evaluation of biochemical activities reported for the nucleoside diphosphate kinase/Nm23/Awd family proteins: opportunities and missteps in understanding their biological functions.Naunyn-Schmiedeberg's archives of pharmacology · 2011Article
- HIV DNA is heavily uracilated, which protects it from autointegration.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Metastasis suppressor function of NM23-H1 requires its 3'-5' exonuclease activity.International journal of cancer · 2011Article
- Structure and Function of the Small MutS-Related Domain.Molecular biology international · 2011Article
- Apurinic/apyrimidinic (AP) site recognition by the 5'-dRP/AP lyase in poly(ADP-ribose) polymerase-1 (PARP-1).Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Making sense of G-quadruplex and i-motif functions in oncogene promoters.The FEBS journal · 2010Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
NM23/NDP kinases play an important role in development and cancer but their biological function is unknown, despite an intriguing collection of biochemical properties including nucleoside-diphosphate kinase (NDP kinase), DNA binding and transcription, a mutator function, and cleavage of unusually structured DNA by means of a covalent enzyme-DNA complex. To assess the role of the nuclease in human NM23-H2, we sought to identify the amino acid responsible for covalent catalysis. By sequencing a DNA-linked peptide and by site-directed mutagenesis, we identified lysine-12, a phylogenetically conserved residue, as the amino acid forming the covalent complex with DNA. In particular, the epsilon-amino group acts as the critical nucleophile, because substitution with glutamine but not arginine completely abrogated covalent adduct formation and DNA cleavage, whereas the DNA-binding properties remained intact. These findings and chemical modification data suggest that phosphodiester-bond cleavage occurs by a DNA glycosylase/lyase-like mechanism known as the signature of base excision DNA repair nucleases. Involvement of NM23/NDP kinase in a DNA repair pathway would be consistent with its role in normal and tumor cell development. Additionally, lysine-12, which is known in the x-ray crystallographic structure to lie in the catalytic pocket involved in the NDP kinase phosphorylation reaction, was found essential also for the NDP kinase activity of NM23-H2, suggesting that the two catalytic activities of NM23-H2 are fundamentally connected.
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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.