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The PARP1/ARTD1-Mediated Poly-ADP-Ribosylation and DNA Damage Repair in B Cell Diversification
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 10 October 2013; in revised form: 6 January 2014 / Accepted: 10 January 2014 / Published: 16 January 2014
Abstract: ADP-ribosylation is an essential post-translational modification, mediated by a family of proteins named poly-ADP-ribose polymerases/Diphtheria toxin-like ADP-ribosyltransferases (PARPs/ARTDs), that functions to assist in cellular homeostasis through an array of mechanisms. Although the function of PARP1/ARTD1-mediated poly-ADP-ribosylation (PARylation) in response to environmental genotoxic stressors has been extensively studied, its role in the regulation and maintenance of cellular events under times of programmed DNA damage and repair remains to be elucidated. In the case of B cell maturation and differentiation, processes such as V(D)J recombination, somatic hypermutation, and class switch recombination, require the induction of DNA strand breaks for the generation of a varied immunoglobulin repertoire and, thus, serve as a model system to explore the function of PARylation in immunological processes. In this review, we summarize the current understanding of ADP-ribosylation and the PARPs/ARTDs family proteins, in particular PARP1/ARTD1-conferred PARylation, in B cells. Following an overview of PARylation in cellular responses to environmental and spontaneous DNA damage, we discuss the emerging function of PARP1/ARTD1 and PARylation in DNA damage-induced nuclear factor kappaB (NF-κB) signaling and B cell maturation and differentiation. Finally, we conclude by underlining further efforts that are needed to understand how the PARPs/ARTDs family proteins and ADP-ribosylation control the development and function of B cells.
Keywords: PARP1/ARTD1; Poly-ADP-ribosylation; PAR; DNA damage; NF-κB; B cells
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Lasola, J.J.; Hodgson, A.; Sun, X.; Wan, F. The PARP1/ARTD1-Mediated Poly-ADP-Ribosylation and DNA Damage Repair in B Cell Diversification. Antibodies 2014, 3, 37-55.
Lasola JJ, Hodgson A, Sun X, Wan F. The PARP1/ARTD1-Mediated Poly-ADP-Ribosylation and DNA Damage Repair in B Cell Diversification. Antibodies. 2014; 3(1):37-55.
Lasola, Jackline J.; Hodgson, Andrea; Sun, Xin; Wan, Fengyi. 2014. "The PARP1/ARTD1-Mediated Poly-ADP-Ribosylation and DNA Damage Repair in B Cell Diversification." Antibodies 3, no. 1: 37-55.