Work

PARP activation promotes nuclear AID accumulation in lymphoma cells

Year: 2016

Type: article

Abstract: // Sandra Tepper 1, * , Julia Jeschke 1, 2, * , Katrin Böttcher 1 , Angelika Schmidt 1 , Kathrin Davari 1 , Peter Müller 1 , Elisabeth Kremmer 3 , Peter Hemmerich 4 , Ines Pfeil 2 , Berit Jungnickel 1, 2 1 Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany 2 Institute of Clinical and Molecular Biology, Helmholtz Center Munich, 81377 Munich, Germany 3 Institute of Molecular Immunology, Helmholtz Center Munich, 81377 Munich, Germany 4 Imaging Facility, Leibniz- Institute on Aging – Fritz Lipmann Institute, 07745 Jena, Germany * These authors have contributed equally to the work Correspondence to: Berit Jungnickel, e-mail: [email protected] Keywords: activation-induced cytidine deaminase, DNA damage, protein stability, poly (ADP-ribose) polymerase, lymphoma Received: July 02, 2015 Accepted: January 12, 2016 Published: February 23, 2016 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.7603