ADP, in the context of DNA, refers to adenosine diphosphate as a component of a larger chemical modification called ADP-ribosylation. This is not ADP in its usual role as an energy carrier within the cell, but rather as a molecule attached to DNA. ADP-ribosylation is a post-translational modification of DNA, meaning it's a chemical change after the DNA molecule is synthesized. It's a crucial process involved in various cellular functions, particularly DNA repair and regulation.
ADP-Ribosylation of DNA: A Closer Look
Several enzymes, primarily poly(ADP-ribose) polymerases (PARPs) such as PARP1, PARP2, PARP3, and PARP10, along with tRNA 2′-phosphotransferase (TRPT1), catalyze the addition of ADP-ribose units to DNA. These enzymes attach ADP-ribose to different sites on the DNA molecule, including thymidine bases and the 5′ and 3′ terminal phosphate residues of DNA strands. The type of ADP-ribosylation (mono or poly) and its location on the DNA influences its function. For instance, poly(ADP-ribose) formation is linked to DNA repair processes, while mono-ADP-ribosylation at DNA ends can be reversed by cellular hydrolases like PARG, MACROD2, TARG1 and ARH3.
- DNA Repair: ADP-ribosylation, particularly poly(ADP-ribosylation) by PARP1 and PARP2, is significantly involved in the cellular response to DNA damage. It acts as a signal to recruit repair proteins to damaged DNA sites.
- Telomere Replication: Studies show that unhydrolyzed DNA-linked ADP-ribose can negatively impact telomere replication and integrity.
- Regulation of Cellular Processes: ADP-ribosylation of DNA and RNA is a widespread modification influencing a variety of cellular processes across all domains of life. This indicates its importance in fundamental biological mechanisms.
The reversible nature of mono-ADP-ribosylation at DNA breaks highlights its role as a dynamic regulatory mechanism, rather than just a static modification.
Examples of ADP-ribosylation in DNA
- DarT–DarG system: The DarT–DarG toxin–antitoxin system involves specific, reversible ADP-ribosylation of thymidine bases in DNA.
- PARP-mediated ADP-ribosylation: PARP enzymes catalyze the addition of ADP-ribose units to DNA, resulting in either mono-ADP-ribosylation or poly(ADP-ribosylation) depending on the enzyme and its target.
