title: Poly(ADP-ribose)polymerase 1 stimulates the AP-site cleavage activity of tyrosyl-DNA phosphodiesterase 1.
abstract: The influence of poly(ADP-ribose)polymerase 1 (PARP1) on the apurinic/apyrimidinic (AP)-site cleavage activity of tyrosyl-DNA phosphodiesterase 1 (TDP1) and interaction of PARP1 and TDP1 were studied. The efficiency of single or clustered AP-site hydrolysis catalysed by TDP1 was estimated. It was shown that the efficiency of AP-site cleavage increases in the presence of an additional AP-site in the opposite DNA strand depending on its position. PARP1 stimulates TDP1; the stimulation effect was abolished in the presence of NAD(+). The interaction of these two proteins was characterized quantitatively by measuring the dissociation constant for the TDP1-PARP1 complex using fluorescently-labelled proteins. The distance between the N-termini of the proteins within the complex was estimated using FRET. The data obtained suggest that PARP1 and TDP1 bind in an antiparallel orientation; the N-terminus of the former protein interacts with the C-terminal domain of the latter. The functional significance of PARP1 and TDP1 interaction in the process of DNA repair was demonstrated for the first time.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrentiev av. 8, Novosibirsk 630090, Russia Department of Natural Sciences, Novosibirsk State University, 2 Pirogov Street, Novosibirsk 630090, Russia.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Lebedeva
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrentiev av. 8, Novosibirsk 630090, Russia Department of Natural Sciences, Novosibirsk State University, 2 Pirogov Street, Novosibirsk 630090, Russia.
authors.forename: Rashid O
authors.initials: RO
authors.lastname: Anarbaev
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrentiev av. 8, Novosibirsk 630090, Russia Department of Natural Sciences, Novosibirsk State University, 2 Pirogov Street, Novosibirsk 630090, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Sukhanova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrentiev av. 8, Novosibirsk 630090, Russia.
authors.forename: Inna A
authors.initials: IA
authors.lastname: Vasil'eva
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrentiev av. 8, Novosibirsk 630090, Russia Department of Natural Sciences, Novosibirsk State University, 2 Pirogov Street, Novosibirsk 630090, Russia.
authors.forename: Nadejda I
authors.initials: NI
authors.lastname: Rechkunova
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Lavrentiev av. 8, Novosibirsk 630090, Russia Department of Natural Sciences, Novosibirsk State University, 2 Pirogov Street, Novosibirsk 630090, Russia lavrik@niboch.nsc.ru.
authors.forename: Olga I
authors.initials: OI
authors.lastname: Lavrik
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D009097:Multienzyme Complexes; D009243:NAD; D004247:DNA; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human
keywords: clustered damages; fluorescently-labelled proteins; poly(ADP-ribose)polymerase 1; protein–protein interaction; tyrosyl-DNA phosphodiesterase 1