Multiple biochemical activities of NM23/NDP kinase in gene regulation.
NM23/NDPk proteins play critical roles in cancer and development; however, our understanding of the underlying biochemical mechanisms is still limited. This large family of highly conserved proteins are known to participate in many events related to DNA metabolism, including nucleotide binding and nucleoside triphosphate synthesis, DNA binding and transcription, and cleavage of DNA strands via covalent protein-DNA complexes. The chemistry of the DNA-cleavage reaction of NM23-H2/NDPk is characteristic of DNA repair enzymes. Both the DNA cleavage and the NDPk reactions are conserved between E. coli and the human enzymes, and several conserved amino acid side chains involved in catalysis are shared by these reactions. It is proposed here that NM23/NDP kinases are important regulators of gene expression during development and cancer via previously unrecognized roles in DNA repair and recombination, and via previously unrecognized pathways and mechanisms of genetic control.
Postel
Edith H
EH
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08546-5414, USA. epostel@molbio.princeton.edu
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; D004247:DNA; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase