Function
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:25043379, PubMed:33186521, PubMed:32028527, PubMed:26344098).
Mediates glutamate, aspartate, serine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD+ is transferred to the acceptor carboxyl group of target 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 (PubMed:7852410, PubMed:9315851, PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836).
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521).
Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:19764761, PubMed:25043379).
Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:33186521, PubMed:32028527).
Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:30257210, PubMed:29954836).
PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600).
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 (PubMed:26344098, PubMed:30356214).
Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR (PubMed:17396150, PubMed:19764761).
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 (PubMed:27471034).
Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272).
PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272).
Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150 (PubMed:19344625).
Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and EEF1A1 (PubMed:17177976).
Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257).
Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257).
Biological Process
Apoptotic process Source: UniProtKB
ATP generation from poly-ADP-D-ribose Source: UniProtKB
Base-excision repair, gap-filling Source: Reactome
Cellular response to amyloid-beta Source: Ensembl
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to insulin stimulus Source: BHF-UCL
Cellular response to oxidative stress Source: MGI
Cellular response to UV Source: BHF-UCL
Cellular response to zinc ion Source: Ensembl
DNA ADP-ribosylation Source: UniProtKB
DNA damage response, detection of DNA damage Source: Ensembl
DNA repair Source: UniProtKB
Double-strand break repair Source: UniProtKB
Double-strand break repair via homologous recombination Source: Reactome
Global genome nucleotide-excision repair Source: Reactome
Macrophage differentiation Source: UniProtKB
Mitochondrial DNA metabolic process Source: MGI
Mitochondrial DNA repair Source: MGI
Mitochondrion organization Source: MGI
Negative regulation of ATP biosynthetic process Source: ParkinsonsUK-UCL
Negative regulation of telomere maintenance via telomere lengthening Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: Reactome
Nucleotide-excision repair, DNA damage recognition Source: Reactome
Nucleotide-excision repair, DNA duplex unwinding Source: Reactome
Nucleotide-excision repair, DNA incision Source: Reactome
Nucleotide-excision repair, DNA incision, 3'-to lesion Source: Reactome
Nucleotide-excision repair, DNA incision, 5'-to lesion Source: Reactome
Nucleotide-excision repair, preincision complex assembly Source: Reactome
Nucleotide-excision repair, preincision complex stabilization Source: Reactome
Peptidyl-glutamic acid poly-ADP-ribosylation Source: UniProtKB
Peptidyl-serine ADP-ribosylation Source: UniProtKB
Positive regulation of cardiac muscle hypertrophy Source: UniProtKB
Positive regulation of double-strand break repair via homologous recombination Source: UniProtKB
Positive regulation of intracellular estrogen receptor signaling pathway Source: Ensembl
Positive regulation of mitochondrial depolarization Source: Ensembl
Positive regulation of myofibroblast differentiation Source: Ensembl
Positive regulation of neuron death Source: Ensembl
Positive regulation of protein localization to nucleus Source: Ensembl
Positive regulation of single strand break repair Source: UniProtKB
Positive regulation of SMAD protein signal transduction Source: Ensembl
Positive regulation of transcription by RNA polymerase II Source: NTNU_SB
Positive regulation of transcription regulatory region DNA binding Source: Ensembl
Protein ADP-ribosylation Source: UniProtKB
Protein auto-ADP-ribosylation Source: UniProtKB
Protein autoprocessing Source: Ensembl
Protein modification process Source: MGI
Protein poly-ADP-ribosylation Source: UniProtKB
Regulation of catalytic activity Source: BHF-UCL
Regulation of cellular protein localization Source: MGI
Regulation of DNA methylation Source: Ensembl
Regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: Ensembl
Regulation of SMAD protein complex assembly Source: Ensembl
Response to aldosterone Source: Ensembl
Response to gamma radiation Source: Ensembl
Signal transduction involved in regulation of gene expression Source: Ensembl
Telomere maintenance Source: BHF-UCL
Transcription by RNA polymerase II Source: ProtInc
Transforming growth factor beta receptor signaling pathway Source: Ensembl
PTM
Poly-ADP-ribosylated on glutamate and aspartate residues by autocatalysis (PubMed:19764761). Poly-ADP-ribosylated by PARP2; poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites (PubMed:19661379). ADP-ribosylated on serine by autocatalysis; serine ADP-ribosylation takes place following interaction with HPF1 (PubMed:28190768). Auto poly-ADP-ribosylated on serine residues, leading to dissociation of the PARP1-HPF1 complex from chromatin (By similarity).
Phosphorylated by PRKDC (PubMed:10467406). Phosphorylated by TXK (PubMed:17177976).
S-nitrosylated, leading to inhibit transcription regulation activity.