DNA ADP-ribosylation

Definition

Target type: biologicalprocess

The covalent attachment of an ADP-ribosyl group to a residue in double-stranded DNA. [PMID:11592983, PMID:27471034, PMID:29361132, PMID:29520010]

DNA ADP-ribosylation is a post-translational modification that involves the attachment of ADP-ribose (ADPR) to proteins. This process is catalyzed by a family of enzymes known as poly(ADP-ribose) polymerases (PARPs). PARPs use nicotinamide adenine dinucleotide (NAD+) as a substrate, cleaving it to release nicotinamide and transferring the ADPR moiety to a target protein. The ADPR can be added as a single unit or as a branched polymer, creating a complex and dynamic modification.

DNA ADP-ribosylation plays a crucial role in various cellular processes, including:

* **DNA repair:** PARPs are activated by DNA damage, and their enzymatic activity is essential for the repair of single-strand breaks (SSBs) and double-strand breaks (DSBs). PARylation creates a scaffold that recruits repair factors to the damaged DNA site, facilitating the repair process.

* **Transcriptional regulation:** PARylation can modulate the activity of transcription factors, either by directly modifying them or by influencing their interactions with other proteins. This can affect the expression of genes involved in DNA repair, cell cycle control, and apoptosis.

* **Signaling pathways:** PARylation participates in various signaling pathways, such as the response to stress, inflammation, and immune activation. PARPs can act as sensors of cellular damage, activating downstream pathways to trigger appropriate cellular responses.

* **Chromatin remodeling:** PARylation can influence chromatin structure, affecting the accessibility of DNA to repair enzymes and other regulatory factors.

The process of DNA ADP-ribosylation is tightly regulated, involving a complex interplay of factors:

* **PARP activation:** Different PARPs are activated by distinct stimuli, such as DNA damage, oxidative stress, and cytokine signaling.

* **Substrate specificity:** PARPs exhibit varying substrate specificity, targeting different proteins and modifying them at specific sites.

* **Polymer chain length:** The length and branching of the ADPR polymer can influence the biological outcome of PARylation, affecting the recruitment of specific repair factors and signaling molecules.

* **PARG activity:** Poly(ADP-ribose) glycohydrolase (PARG) is an enzyme that removes ADPR from proteins, acting as a "de-PARylase" to regulate the duration and extent of PARylation.

Dysregulation of DNA ADP-ribosylation is implicated in various disease states, including cancer, neurodegenerative disorders, and inflammatory diseases. Understanding the intricate details of this modification is crucial for developing novel therapeutic strategies targeting PARP activity in these conditions.'
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Proteins (4)

Compounds (55)