Drosophila Uri, a PP1α binding protein, is essential for viability, maintenance of DNA integrity and normal transcriptional activity

URI (unconventional prefoldin RPB5 interactor) is a conserved molecular chaperone implicated in a variety of cellular processes, including the transcriptional response to nutrient signalling and maintenance of DNA integrity. We show that Drosophila Uri binds PP1α with much higher affinity than PP1β, and that this ability to discriminate between PP1c forms is conserved to humans. Most Uri is cytoplasmic, however we found some protein associated with active RNAPII on chromatin. We generated a uri loss of function allele, and show that uri is essential for viability in Drosophila. uri mutants have transcriptional defects, reduced cell viability and differentiation in the germline, and accumulate DNA damage in their nuclei.Uri is the first PP1α specific binding protein to be described in Drosophila. Uri protein plays a role in transcriptional regulation. Activity of uri is required to maintain DNA integrity and cell survival in normal development.Biochemical analysis of protein phosphatase activity led to the identification of distinct enzyme classes based on sensitivity to inhibitors, in vitro substrate specificity and cation requirements. Type 1 protein phosphatase (PP1) is one of the major serine/threonine phosphatase classes found in all eukaryotic cells. Cloning of the catalytic subunits of PP1 (PP1c) revealed that there are distinct enzyme forms which had not been distinguished biochemically. Phylogenetic analysis has revealed that there is an evolutionarily conserved distinction between animal PP1α (human PP1α and γ; Drosophila PP1α87B, PP1α13C and PP1α96A) and PP1β (human PP1β or PP1δ; Drosophila PP1β9C) implying that the gene products have distinct biological functions despite their identical biochemical properties in vitro and >85% sequence identity [1]. In Drosophila larvae, PP1α87B provides 80% of the total PP1 catalytic activity [2], with 10% each being attributed to PP1α96A and PP1β9C [3]. PP1α87B and PP1β9C are both essential for viability, however PP1α96