Human Poly [Adp-Ribose] Polymerase 1, PARP1 ELI

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).