Abstract
Problem statement: Dictyostelium discoideum, a unicellular eukaryote, exhibits multicellularity upon nutrient starvation, making it a better model for developmental studies and for the study of various signal transduction pathways. The most felicitous point of interest is that many of its genes show high degree of similarity to vertebrate genes. Poly (ADP-ribose) polymerase (PARP), a ubiquitous and abundant nuclear protein, has a number of distinct biochemical activities well suited for both structural and regulatory roles throughout its life cycle. We have analysed structural and evolutionary significance of PARP. Approach: D. discoideum lacks caspases and hence it exhibits caspase independent cell death which is of unique interest. PARP is a key protein involved in cell death in D. discoideum. An in silico approach to study the domain organization of PARP’s in D. discoideum would help us to understand evolution of the structural pattern from prokaryotes to eukaryotes. Results: Our previous studies showed involvement of PARP in D. discoideum cell death and development. We have attempted to probe the significance of PARPs in D. discoideum using bioinformatics approach. In this organism PARPs are encoded by 8 members whereas in H. sapiens there are 17 such members encoding PARP family. Conclusion: Our analysis suggests out of 8 genes, adprt1a and adprt1b seem to be involved in DNA damage response. Our approach with different bioinformatics tools suggests that these proteins also show homology with the H. sapiens counterparts. This article summarizes the domain organization of PARPs to throw light on the biological role of these proteins which will be helpful for further experimental studies in our model organism.
Highlights
DNA damaging agents like ROS, MNNG and UV irradiation are known to activate Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme that has various physiological functions (Rajawat et al, 2007; Burkle, 2001; De et al, 1994; Lautier et al, 1993; Shall and Murcia, 2000; Vodenicharov et al, 2005)
In response to DNA damage, PARP-1 uses NAD+ as a substrate and attaches polymers of ADP-ribose on different acceptor proteins or on PARP-1 itself, resulting into a branched polymer known as PAR (Poly ADP-ribose) which can be covalently linked mainly to glutamic acid residues (Hakme et al, 2008) of acceptor proteins i.e., the polymerization starts at a glutamic acid residue (Skalitzky et al, 2003)
Associated proteins often have similar phylogenetic profiles and conserved amino acids (Sanchez-Aguilar et al, 2007). It has been Fig. 13: Evolution of PARP protein experimentally proved that this organism does not have caspases (Olie et al, 1998) which is seen in the
Summary
DNA damaging agents like ROS, MNNG and UV irradiation are known to activate PARP, a nuclear enzyme that has various physiological functions (Rajawat et al, 2007; Burkle, 2001; De et al, 1994; Lautier et al, 1993; Shall and Murcia, 2000; Vodenicharov et al, 2005). Its genome consists of 34 Mb of DNA which is compacted into six chromosomes ranging from 4-7 Mb each (Eichinger et al, 2005) It comprises of nearly 8,000-10,000 genes and the most interesting point is that many of the genes show high degree of similarity with those of higher organisms. Structural studies with different bioinformatics tools revealed high homology of D. discoideum PARPs with those of H. sapiens. BLAST (Altschul et al, 1990) analysis shows that ADPRT1A and ADPRT1B of D. discoideum show ~50% similarity to human PARP-1 (Fig. 1 and 2)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call