title: Characterization of the DNA dependent activation of human ARTD2/PARP2.
abstract: Human ADP-ribosyltransferase 2 (ARTD2/PARP2) is an enzyme catalyzing a post-translational modification, ADP-ribosylation. It is one of the three DNA dependent ARTDs in the 17 member enzyme family. ADP-ribosylation catalyzed by ARTD2 is involved in the regulation of multiple cellular processes such as control of chromatin remodeling, transcription and DNA repair. Here we used a combination of biochemical and biophysical methods to elucidate the structure and function of ARTD2. The solution structures revealed the binding mode of the ARTD2 monomer and dimer to oligonucleotides that mimic damaged DNA. In the complex, DNA binds between the WGR domain and the catalytic fragment. The binding mode is supported by biophysical data that indicate all domains contribute to DNA binding. Also, our study showed that ARTD2 is preferentially activated by short 5'-phosphorylated DNA oligonucleotides. We demonstrate that the N-terminus functions as a high-affinity DNA-binding module, while the WGR domain contributes to DNA binding specificity and subsequent catalytic activation. Our data further suggest that ARTD2 would function in double strand break repair as a dimeric module, while in single strand break repair it would function as a monomer.
authors.affiliation: Faculty of Biochemistry and Molecular Medicine &Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Ezeogo
authors.initials: E
authors.lastname: Obaji
authors.affiliation: Faculty of Biochemistry and Molecular Medicine &Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Haikarainen
authors.affiliation: Faculty of Biochemistry and Molecular Medicine &Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Lari
authors.initials: L
authors.lastname: Lehtiö
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D004789:Enzyme Activation; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000378:metabolism; D055503:Protein Multimerization
chemical_list: D009841:Oligonucleotides; D004247:DNA; C483041:PARP2 protein, human; D011065:Poly(ADP-ribose) Polymerases