Oncotarget

Research Papers:

PARP activation promotes nuclear AID accumulation in lymphoma cells

Sandra Tepper _, Julia Jeschke, Katrin Böttcher, Angelika Schmidt, Kathrin Davari, Peter Müller, Elisabeth Kremmer, Peter Hemmerich, Ines Pfeil and Berit Jungnickel

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Oncotarget. 2016; 7:13197-13208. https://doi.org/10.18632/oncotarget.7603

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Abstract

Sandra Tepper1,*, Julia Jeschke1,2,*, Katrin Böttcher1, Angelika Schmidt1, Kathrin Davari1, Peter Müller1, Elisabeth Kremmer3, Peter Hemmerich4, Ines Pfeil2, Berit Jungnickel1,2

1Department of Cell Biology, Institute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, 07745 Jena, Germany

2Institute of Clinical and Molecular Biology, Helmholtz Center Munich, 81377 Munich, Germany

3Institute of Molecular Immunology, Helmholtz Center Munich, 81377 Munich, Germany

4Imaging 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.


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