In the context of DNA, ADP refers to adenosine diphosphate as a component of ADP-ribosylation. ADP-ribosylation is a crucial chemical modification of DNA, not a structural component like the nucleotides adenine, guanine, cytosine, and thymine. This modification involves the attachment of ADP-ribose units to DNA. It's a post-translational modification, meaning it occurs after the DNA molecule is synthesized.
The Role of ADP-Ribosylation in DNA
Several enzymes, notably PARP1 and PARP2 (poly(ADP-ribose) polymerases), catalyze ADP-ribosylation in response to DNA damage. This process plays a vital role in DNA repair mechanisms. The addition of ADP-ribose can alter the structure and function of DNA, influencing processes like:
- DNA repair: ADP-ribosylation helps recruit and activate proteins involved in repairing damaged DNA. [Reference: ADP-ribosylation is a widespread posttranslational modification that is of particular therapeutic relevance due to its involvement in DNA repair.]
- Telomere maintenance: Studies indicate that unhydrolyzed DNA-linked ADP-ribose can negatively affect telomere replication and integrity. [Reference: We demonstrate that unhydrolyzed DNA-linked ADP-ribose compromises telomere replication and telomere integrity.]
- Regulation of cellular processes: ADP-ribosylation is not limited to DNA; it also modifies RNA and other macromolecules, impacting various cellular processes. [Reference: ADP-ribosylation is a chemical modification of macromolecules found across all domains of life and known to regulate a variety of cellular processes.]
Specific ADP-ribosylation can occur on thymidine bases within the DNA through the DarT–DarG toxin–antitoxin system. This is a reversible process. [Reference: Here we present evidence that specific, reversible ADP-ribosylation of DNA on thymidine bases occurs in cellulo through the DarT–DarG toxin–antitoxin system.] Moreover, different enzymes like PARP1–3, PARP10, and TRPT1 can catalyze ADP-ribosylation of both DNA and RNA. [Reference: RNA and DNA can be ADP-ribosylated by specific ADP-ribosyltransferases such as PARP1–3, PARP10 and tRNA 2′-phosphotransferase (TRPT1).]
Types of ADP-Ribosylation
Different types of ADP-ribosylation exist, including:
- Mono-ADP-ribosylation: The addition of a single ADP-ribose unit.
- Poly(ADP-ribosyl)ation: The addition of multiple ADP-ribose units forming a polymer chain.
These modifications have distinct effects on DNA structure and function. The process is reversible, with cellular hydrolases like PARG, MACROD2, TARG1, and ARH3 removing ADP-ribose units. [Reference: We further show that mono ADP-ribosylation at DNA ends can be efficiently reversed by several cellular hydrolases (PARG, MACROD2, TARG1 and ARH3).]
