Robust immunoglobulin class switch recombination and end joining in Parp9‐deficient mice

Abstract

To mount highly specific and adapted immune responses, B lymphocytes assemble and diversify their antibody repertoire through mechanisms involving the formation of programmed DNA damage. Immunoglobulin class switch recombination (CSR) is triggered by DNA lesions induced by activation-induced cytidine deaminase, which are processed to double-stranded DNA break (DSB) intermediates. These DSBs activate the cellular DNA damage response and enroll numerous DNA repair factors, involving poly(ADP-ribose) polymerases Parp1, Parp2, and Parp3 to promote appropriate DNA repair and efficient long-range recombination. The macroParp Parp9, which is overexpressed in certain lymphomas, has been recently implicated in DSB repair, acting together with Parp1. Here, we examine the contribution of Parp9 to the resolution of physiological DSBs incurred during V(D)J recombination and CSR by generating Parp9 mice. We find that Parp9-deficient mice are viable, fertile, and do not show any overt phenotype. Moreover, we find that Parp9 is dispensable for B-cell development. Finally, we show that CSR and DNA end-joining are robust in the absence of Parp9, indicating that Parp9 is not essential in vivo to achieve physiological DSB repair, or that strong compensatory mechanisms exist.

A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair

“…It is well known that the 53BP1 protein is also a factor that plays a role in Igh class switch recombination (CSR) in B lymphocytes and is an essential target for sensitizing BRCA1-deficient tumors to PARP inhibitors [143]. 53BP1 contributes to DNA repair and the orientation of the broken DNA ends during class-switch recombination [144,145].…”

Molecular mimicry may explain multi-organ damage in COVID-19

“…2. Poly (ADP-Ribose) Polymerase Family Member 9 (PARP9), also known as mono-ADP-ribosyltransferase (ARTD)-9, is a protein involved in differentiation and function of immune cells such as B lymphocytes [7] and macrophages [8].…”

Development of prognostic indicator based on NAD+ metabolism related genes in glioma

“…An enquiry into the functional status of biomarkers in glioma showed that PARP9 was positively associated with EMT, cell metastasis and cell differentiation and negatively associated with DNA damage. It has been shown that PARP9 was essential for B cell development ( 43 ). In addition, the PARP inhibitor veliparib could act on DNA damage repair in prostate cancer cells ( 44 ), which supported our study.…”