title: PARP activation promotes nuclear AID accumulation in lymphoma cells.
abstract: Activation-induced cytidine deaminase (AID) initiates immunoglobulin diversification in germinal center B cells by targeted introduction of DNA damage. As aberrant nuclear AID action contributes to the generation of B cell lymphoma, the protein's activity is tightly regulated, e.g. by nuclear/cytoplasmic shuttling and nuclear degradation. In the present study, we asked whether DNA damage may affect regulation of the AID protein. We show that exogenous DNA damage that mainly activates base excision repair leads to prevention of proteasomal degradation of AID and hence its nuclear accumulation. Inhibitor as well as knockout studies indicate that activation of poly (ADP-ribose) polymerase (PARP) by DNA damaging agents promotes both phenomena. These findings suggest that PARP inhibitors influence DNA damage dependent AID regulation, with interesting implications for the regulation of AID function and chemotherapy of lymphoma.
authors.affiliation: Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Tepper
authors.affiliation: Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany.|Institute of Clinical and Molecular Biology, Helmholtz Center Munich, 81377 Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Jeschke
authors.affiliation: Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Böttcher
authors.affiliation: Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Davari
authors.affiliation: Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Müller
authors.affiliation: Institute of Molecular Immunology, Helmholtz Center Munich, 81377 Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Imaging Facility, Leibniz- Institute on Aging - Fritz Lipmann Institute, 07745 Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hemmerich
authors.affiliation: Institute of Clinical and Molecular Biology, Helmholtz Center Munich, 81377 Munich, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Pfeil
authors.affiliation: Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany.|Institute of Clinical and Molecular Biology, Helmholtz Center Munich, 81377 Munich, Germany.
authors.forename: Berit
authors.initials: B
authors.lastname: Jungnickel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003564:Cytidine Deaminase / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: DNA damage; activation-induced cytidine deaminase; lymphoma; poly (ADP-ribose) polymerase; protein stability