Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR. Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity. Probably also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Catalyzes the poly-ADP-ribosylation of histones in a HPF1-dependent manner. Involved in the base excision repair (BER) pathway by catalyzing the poly-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Note: This description may include information from UniProtKB.
Protein type: DNA repair, damage; EC 22.214.171.124; Nuclear envelope; Nuclear receptor co-regulator; Nucleolus; Transferase
Cellular Component: mitochondrion; nuclear envelope; nucleolus; nucleoplasm; nucleus; protein-containing complex; protein-DNA complex; site of DNA damage; site of double-strand break; transcription factor complex
Molecular Function: DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; enzyme binding; estrogen receptor binding; histone deacetylase binding; identical protein binding; NAD binding; NAD+ ADP-ribosyltransferase activity; protein ADP-ribosylase activity; protein binding; protein kinase binding; protein N-terminus binding; R-SMAD binding; RNA polymerase II regulatory region sequence-specific DNA binding; transcription factor binding; zinc ion binding
Biological Process: apoptotic process; ATP generation from poly-ADP-D-ribose; cellular response to amyloid-beta; cellular response to DNA damage stimulus; cellular response to insulin stimulus; cellular response to oxidative stress; cellular response to UV; cellular response to zinc ion; DNA ADP-ribosylation; DNA damage response, detection of DNA damage; DNA repair; double-strand break repair; double-strand break repair via homologous recombination; global genome nucleotide-excision repair; macrophage differentiation; mitochondrial DNA metabolic process; mitochondrial DNA repair; mitochondrion organization; negative regulation of ATP biosynthetic process; negative regulation of telomere maintenance via telomere lengthening; negative regulation of transcription by RNA polymerase II; nucleotide-excision repair, DNA damage recognition; nucleotide-excision repair, DNA duplex unwinding; nucleotide-excision repair, DNA incision; nucleotide-excision repair, DNA incision, 3'-to lesion; nucleotide-excision repair, DNA incision, 5'-to lesion; nucleotide-excision repair, preincision complex assembly; nucleotide-excision repair, preincision complex stabilization; peptidyl-glutamic acid poly-ADP-ribosylation; peptidyl-serine ADP-ribosylation; positive regulation of cardiac muscle hypertrophy; positive regulation of double-strand break repair via homologous recombination; positive regulation of intracellular estrogen receptor signaling pathway; positive regulation of mitochondrial depolarization; positive regulation of myofibroblast differentiation; positive regulation of neuron death; positive regulation of protein localization to nucleus; positive regulation of single strand break repair; positive regulation of SMAD protein signal transduction; positive regulation of transcription by RNA polymerase II; positive regulation of transcription regulatory region DNA binding; protein ADP-ribosylation; protein auto-ADP-ribosylation; protein autoprocessing; protein modification process; protein poly-ADP-ribosylation; regulation of catalytic activity; regulation of cellular protein localization; regulation of DNA methylation; regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; regulation of SMAD protein complex assembly; response to aldosterone; response to gamma radiation; signal transduction involved in regulation of gene expression; telomere maintenance; transcription by RNA polymerase II; transforming growth factor beta receptor signaling pathway