The key difference between PARP1 and PARP2 is that plant and animal PARP1 carry Zn-finger DNA binding motifs while plant PARP2 carries N-terminal SAP DNA binding motifs.
Poly ADP ribose polymerase (PARP) is a family of proteins that are nuclear enzymes. There are 17 different types of PARP enzymes in the PARP family. PARP1 and PARP2 are two enzymes essential to normal DNA repair activities.
CONTENTS
1. Overview and Key Difference
2. What is PARP
3. What is PARP1
4. What is PARP2
5. Similarities Between PARP1 and PARP2
6. Side by Side Comparison – PARP1 vs PARP2 in Tabular Form
7. Summary
What is PARP?
PARP (Poly ADP ribose polymerase) is a family of proteins that serve in numerous cellular processes like DNA repair, genomic stability, and programmed cell death. They catalyze a process called ADP-ribosylation. ADP-ribosylation refers to the addition of ADP-ribose units from nicotinamide adenine dinucleotide (NAD) to target substrates in order to repair the DNA strand breaks.
PARP enzymes are DNA-binding proteins. They are activated by the nicks present in DNA molecules. Once they bind with DNA breaks, they hydrolyze NAD+ into nicotinamide and promote the polymerization of the ADP-ribose. Therefore, PARP nuclear enzymes participate in DNA repair. Moreover, poly-ADP-ribosylation works as a post-translational modification that plays a key role in replication, transcriptional regulation, telomere maintenance and protein degradation. PARP enzymes also participate in the maintenance of genome stability, regulation of chromatin structure, cell proliferation, and apoptosis.
What is PARP1?
PARP1 is a member of the PARP protein family. It is the first and best-characterized protein in this family. It acts as a first responder that detects DNA damages and then facilitates the choice of repairing mechanism. Moreover, PARP1 regulates the repair of single-strand DNA damages.
Figure 01: PARP1
In addition to repairing single-strand DNA breaks, PARP1 regulates replication fork progression and restart. Furthermore, it promotes alternative non-homologous end-joining.
What is PARP2?
PARP2 is another member protein in PARP protein family. It is closely related to PARP1 enzyme. The gene PARP2 codes for PARP2 protein in humans. PARP2 has a catalytic domain but lacks N terminal DNA binding domain. PARP inhibitor anti-cancer drugs can inhibit PARP2, similar to PARP1.
Figure 02: PARP2
In plants, especially in Arabidopsis thaliana, PARP2 plays a significant role in protective responses to DNA damage and bacterial pathogenesis than PARP1.
What are the Similarities Between PARP1 and PARP2?
- PARP1 and PARP2 are two types of nuclear enzymes.
- They use NAD+ as their substrate to catalyze poly ADP ribosylation.
- Both are activated by DNA single-strand breaks.
- Mammalian PARP1 and PARP2 are located in the nucleus.
- Both PARP1 and PARP2 interact with chromatin.
- They repair DNA damages.
- Some PARP inhibitor anti-cancer drugs aimed at PARP1 also inhibit PARP2.
What is the Difference Between PARP1 and PARP2?
PARP1 is a member of the PARP protein family which has a catalytic domain and N-terminal DNA binding domain while PARP2 is a member of the PARP family which lacks N-terminal DNA binding domain. The key difference between PARP1 and PARP2 is that plant and animal PARP1 carry Zn-finger DNA binding motifs while plant PARP2 carries N-terminal SAP DNA binding motifs.
The following infographic summarizes the difference between PARP1 and PARP2.
Summary – PARP1 vs PARP2
PARPs are nuclear enzymes that sense DNA damages and repair them. PARP1 and PARP2 are two of them which are closely related. Both enzymes have a catalytic domain. But PARP2 lacks N-terminal DNA binding domain which is present in PARP1. Thus, this is the key difference between PARP1 and PARP2. Both types of enzymes use NAD+ as their substrate.
Reference:
1. “Poly ADP Ribose Polymerase – An Overview | Sciencedirect Topics”. Sciencedirect.Com, 2020, Available here.
2. Julio C. Morales, David A. Boothman. “Review Of Poly (ADP-Ribose) Polymerase (PARP) Mechanisms Of Action And Rationale For Targeting In Cancer And Other Diseases”. Pubmed Central (PMC), 2020, Available here.
Image Courtesy:
1. “Protein PARP1 PDB 1uk0” By Emw – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Protein PARP2 PDB 1gs0” By Emw – Own work (CC BY-SA 3.0) via Commons Wikimedia