title: T4 DNA ligase synthesizes dinucleoside polyphosphates.
abstract: T4 DNA ligase (EC 6.5.1.1), one of the most widely used enzymes in genetic engineering, transfers AMP from the E-AMP complex to tripolyphosphate, ADP, ATP, GTP or dATP producing p4A, Ap3A, Ap4A, Ap4G and Ap4dA, respectively. Nicked DNA competes very effectively with GTP for the synthesis of Ap4G and, conversely, tripolyphosphate (or GTP) inhibits the ligation of DNA by the ligase. As T4 DNA ligase has similar requirements for ATP as the mammalian DNA ligase(s), the latter enzyme(s) could also synthesize dinucleoside polyphosphates. The present report may be related to the recent finding that human Fhit (fragile histidine triad) protein, encoded by the FHIT putative tumor suppressor gene, is a typical dinucleoside 5',5''-P1,P3-triphosphate (Ap3A) hydrolase (EC 3.6.1.29).
authors.affiliation: Departamento de Bioquímica, Instituto de Investigaciones Biomédicas, CSIC, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Madrid
authors.forename: D
authors.initials: D
authors.lastname: Martín
authors.forename: E A
authors.initials: EA
authors.lastname: Atencia
authors.forename: A
authors.initials: A
authors.lastname: Sillero
authors.forename: M A
authors.initials: MA
authors.lastname: Günther Sillero
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D017122:Bacteriophage T4 / Q000201:enzymology; D011088:DNA Ligases / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000096:biosynthesis* / Q000302:isolation & purification; D016147:Genes, Tumor Suppressor; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism; D013379:Substrate Specificity; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D011088:DNA Ligases; D015226:Dinucleoside Phosphates; D009363:Neoplasm Proteins; D011506:Proteins; D012265:Ribonucleotides; D000099170:Bis(5'-adenosyl)triphosphatase