poly(ADP-ribose) glycohydrolase activity

Definition

Target type: molecularfunction

Catalysis of the hydrolysis of poly(ADP-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-ribose. [EC:3.2.1.143]

Poly(ADP-ribose) glycohydrolase (PARG) activity is an essential enzymatic function involved in the regulation of cellular processes, primarily DNA repair and programmed cell death. PARG enzymes hydrolyze poly(ADP-ribose) (PAR) chains, which are branched polymers attached to proteins, specifically to DNA repair proteins and histones, in response to DNA damage. This enzymatic activity plays a crucial role in the following ways:

1. **DNA Repair:** PARylation, the process of adding PAR chains, is triggered by DNA damage. PARG removes these chains, allowing DNA repair proteins to access the damaged DNA and initiate repair mechanisms. This precise regulation of PARylation and PARG activity ensures efficient DNA repair and prevents genomic instability.

2. **Cell Death and Survival:** PARG activity is also critical in determining cell fate. In response to severe DNA damage, PARG can promote cell death by removing PAR chains from PARP1, a key regulator of apoptosis. Conversely, PARG can also promote cell survival by facilitating DNA repair and preventing excessive PAR accumulation, which can be detrimental to cell function.

3. **Chromatin Remodeling:** PARG activity is involved in chromatin remodeling, the process of altering the structure of chromatin, the complex of DNA and proteins that makes up chromosomes. PARylation can affect chromatin accessibility, and PARG regulates this process by removing PAR chains, influencing gene expression and other cellular processes.

4. **Signal Transduction:** PARG activity is implicated in signal transduction pathways, specifically those involved in cellular stress responses and inflammation. By regulating PARylation levels, PARG contributes to the activation or inhibition of signaling molecules, influencing downstream cellular responses.

In summary, PARG activity plays a multifaceted role in maintaining genomic stability, regulating cell fate, and influencing various cellular processes. Its ability to remove PAR chains provides a fine-tuned mechanism for controlling the activity of DNA repair proteins, promoting cell survival or death, and modulating chromatin dynamics. Dysregulation of PARG activity can contribute to various diseases, including cancer and neurodegenerative disorders.'
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Proteins (3)

Compounds (2)