PARP3

Description

The PARP3 (poly(ADP-ribose) polymerase family member 3) is a protein-coding gene located on chromosome 3.

Poly [ADP-ribose] polymerase 3 is an enzyme that in humans is encoded by the PARP3 gene. The protein encoded by this gene belongs to the PARP family. These enzymes modify nuclear proteins by poly-ADP-ribosylation, which is required for DNA repair, regulation of apoptosis, and maintenance of genomic stability. This gene encodes the poly(ADP-ribosyl)transferase 3, which is preferentially localized to the daughter centriole throughout the cell cycle. Alternatively spliced transcript variants encoding different isoforms have been identified.

PARP3 is a mono-ADP-ribosyltransferase that adds a single ADP-ribose moiety to target proteins, playing a critical role in the cellular response to DNA damage. It modifies glutamate, aspartate, or lysine residues on its targets, unlike PARP1 and PARP2, which can add multiple ADP-ribose units. PARP3 participates in DNA repair by attaching ADP-ribose to key proteins involved in chromatin structure and DNA metabolism, such as histone H2B, XRCC5, and XRCC6. This modification occurs after DNA damage and serves as a crucial signal for activating DNA repair pathways. PARP3 is particularly important in single-strand break repair, where it modifies histone H2B on 'Glu-2' in nucleosomes containing damaged DNA. It also collaborates with the Ku80-Ku70 complex to limit end-resection during non-homologous end-joining (NHEJ), promoting accurate repair. Additionally, PARP3 suppresses G-quadruplex structures formed in response to DNA damage. It interacts with various DNA repair factors and plays a role in responding to both exogenous and endogenous DNA breaks. PARP3 works with APLF to maintain the LIG4-XRCC4 complex on chromatin, accelerating DNA ligation during NHEJ. It may also connect the DNA damage surveillance network to the mitotic fidelity checkpoint. PARP3 acts as a negative regulator of immunoglobulin class switch recombination, likely by controlling the levels of AICDA/AID on chromatin. Beyond proteins, PARP3 can also modify DNA, adding a single ADP-ribose moiety to 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks. PARP3 interacts with PARP1, potentially activating it in the absence of DNA damage. It also interacts with PRKDC, XRCC5/Ku80, XRCC6/Ku70, EZH2, HDAC1, HDAC2, SUZ12, YY1, LRIG3, and LIG4.

PARP3 is also known as ADPRT3, ADPRTL2, ADPRTL3, ARTD3, IRT1, PADPRT-3.

Associated Diseases

WES Whole Exome Sequencing