MAPK - PARP1
Poly(ADP-ribose) polymerase 1 (PARP1) is a crucial DNA repair enzyme that plays a key role in the cellular response to DNA damage. It catalyzes poly(ADP-ribosyl)ation (PARylation), a post-translational modification that regulates DNA repair, gene expression, and cell survival.
DNA Damage-Dependent PARylation Process by PARP1
The activation of PARP1 and its PARylation reaction is a multi-step process, which includes:
DNA Damage Recognition
Upon single-strand breaks (SSBs) or double-strand breaks (DSBs), PARP1 binds to damaged DNA via its zinc finger domains (Zn fingers).
This binding induces a conformational change that activates its catalytic domain.
NAD⁺ Binding and Hydrolysis
Activated PARP1 utilizes NAD⁺ (nicotinamide adenine dinucleotide) as a substrate.
It cleaves NAD⁺ to release nicotinamide and generate an ADP-ribose unit.
Attachment of ADP-Ribose Monomers
The initial ADP-ribose unit is covalently attached to PARP1 itself or other target proteins, such as histones and DNA repair factors.
Poly(ADP-Ribose) Chain Elongation
PARP1 continues to catalyze the transfer of multiple ADP-ribose units, forming linear or branched poly(ADP-ribose) (PAR) chains.
This modification recruits DNA repair complexes, facilitating base excision repair (BER) and homologous recombination (HR).
Regulation of Target Proteins
PAR chains act as a platform for protein-protein interactions, modulating DNA repair, chromatin remodeling, and transcriptional regulation.
PARP1 Auto-Regulation and PAR Degradation
Once DNA repair is complete, poly(ADP-ribose) glycohydrolase (PARG) degrades PAR chains.
This restores cellular homeostasis and prevents excessive PARP1 activity.
Shop By
Catalog No.
Product Name
Application
Product Information
Citations
-
PARP-1 inhibitor
TAK1/MAP4K2 inhibitor 1 is a potent dual inhibitor targeting transforming growth factor β-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2), exhibiting IC₅₀ values of 41.1 nM and 18.2 nM, respectively.
