Poly ADP ribose polymerase

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Identifiers
EC number	2.4.2.30
CAS number	9077-69-8
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Poly ADP-ribose polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death. The main function of PARP is to detect and initiate an immediate cellular response to metabolic stress, DNA damage, and inflammation.

Function

PARP is a enzyme that uses nicotinamide adenine dinucleotide (NAD+) as a substrate to transfer ADP-ribose units to target proteins. This process, known as ADP-ribosylation, plays a key role in regulating cellular processes by altering the function of the modified proteins. The most well-known role of PARP is its involvement in the repair of single-strand breaks in DNA. If these breaks are not repaired, they can lead to the formation of double-strand breaks when the DNA replicates, which can be catastrophic for the cell.

Mechanism

Upon sensing strand breaks in DNA, PARP binds to the DNA and synthesizes a poly(ADP-ribose) (PAR) chain as a signal to recruit other DNA repair proteins to the site of damage. This activity is crucial for the base excision repair pathway, a mechanism that corrects single-strand breaks that occur through oxidative stress or normal metabolic processes.

Clinical Significance

PARP inhibitors are a class of pharmacological inhibitors that have a potent effect on PARP and have shown promise in treating several types of cancers, particularly those deficient in other DNA repair mechanisms, such as BRCA1 and BRCA2 mutations in breast and ovarian cancers. By inhibiting PARP, these drugs cause an accumulation of DNA damage in cancer cells, leading to cell death.

Types of PARP

There are several members of the PARP family, each with a slightly different role in cellular processes. PARP1, the most abundant and best-studied, is primarily involved in DNA repair. Other members, like PARP2 and PARP3, have roles in maintaining the stability of the genome and in the regulation of programmed cell death.

Research

Research on PARP continues to be a highly active area, focusing not only on cancer therapy but also on the potential roles of PARP in other diseases such as cardiovascular diseases, neurodegenerative diseases, and inflammatory conditions.

See Also

• DNA repair
• Oncology
• Pharmacology