omes. The eukaryotic Romidepsin supplier supergroup Amoebozoa is represented by only one species, Dictyostelium discoideum, while there are no representatives of Rhizaria sequenced. Despite the limitations of the available sequences, we have identified unique types of PARPs in Naegleria gru beri, Trichomonas vaginalis and green algae and clarified the phylogenetic distribution of tankyrases. There are likely to be additional variations of PARPs discovered as more eukaryotic genomes are sequenced and a further advancement of our understanding of evolution of this important proteins superfamily. Clade 5 and vaults The Clade 5 PARPs have a limited phylogenetic distri bution, found only in a subset of animals and amoeba. vPARP was originally identified in a two hybrid screen using the major vault protein pro tein as bait and shown to act as a bona fide PARP.

vPARP associates not only with the ribonucleoprotein vault complex, but also can be found in the nucleus, associated with the telomere and the mitotic spindle. The function of vPARP at any of its locations is unclear. Vaults have been best studied in mammals and in these organisms are composed of three proteins, MVP, TEL1, and vPARP. In addition, sev eral vault specific RNAs are found. The func tion or functions of vaults are still unclear, they are associated with drug resistance and several signalling pathways, as well as the nuclear pore complex. vPARP deficient mice are normal and fertile with no defects in telomeres or vaults. More recently these mice have been found to develop more tumours in response to carcinogens, suggesting a role in chemically induced cancers.

Vaults have been identified in diverse animals and in other eukaryotes such as the amoeba Dictyostelium dis coideum, flatworms, and trypanosomatides. However, vaults appear to be missing from fungi, a number of model animals and in plants. The fact that vPARP does not appear essential for normal development or vault structure in mouse suggests that this protein is not essential for vault func tion. This may explain why organisms that have been demonstrated to contain vaults in their cells do not always encode proteins that look like vPARP. Clade 2 plant specific PARPs are involved in stress responses In addition to containing three Clade 1 PARPs through out and Clade 6 PARPs only in the bryophytes, the land plants contain a unique clade of PARP like proteins.

This clade can be subdivided into two subclades, one of which contains proteins with an N terminal WWE domain. Clade 2 is distinct from Clade 3, which also contains proteins with WWE domains. Batimastat A group within Clade 2, confined to the eudicots within the angios perms, consists of truncated proteins lacking the N terminal WWE domain. Examination of the phylogeny of Clade 2 clearly illustrates the importance of genome duplication during plant evolution, plant spe cies tend to encode gene pairs. The plant Clade 2 proteins have only been investi gated in the model angiosperm http://www.selleckchem.com/products/Vandetanib.html Arabidopsis thaliana. Arab