ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses ( , ). Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose) . In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones . During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 . Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (, ). In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ); the complex function is negatively modulated by PARP9 activity . Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (By similarity). In macrophages, positively regulates pro-inflammatory cytokines production in response to IFNG stimulation by suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting STAT1 phosphorylation . Also suppresses PARP14-mediated STAT6 ADP-ribosylation .
Subcellular locations: Cytoplasm, Cytosol, Nucleus
Shuttles between the nucleus and the cytosol . Translocates to the nucleus in response to IFNG or IFNB1 stimulation . Export to the cytosol depends on the interaction with DTX3L . Localizes at sites of DNA damage in a PARP1-dependent manner (, ).
Expressed in lymphocyte-rich tissues, spleen, lymph nodes, peripheral blood lymphocytes and colonic mucosa (, ). Expressed in macrophages . Also expressed in nonhematopoietic tissues such as heart and skeletal muscle (, ). Isoform 2 is the predominant form . Most abundantly expressed in lymphomas with a brisk host inflammatory response (, ). In diffuse large B-cell lymphomas tumors, expressed specifically by malignant B-cells (, ).