title: Drosophila Rif1 is an essential gene and controls late developmental events by direct interaction with PP1-87B.
abstract: Rif1, identified as a regulator of telomerase in yeast, is an evolutionarily conserved protein and functions in diverse processes including telomere length regulation, epigenetic gene regulation, anti-checkpoint activity, DNA repair and establishing timing of firing at replication origins. Previously we had identified that all Rif1 homologues have PP1 interacting SILK-RVxF motif. In the present study, we show that Drosophila Rif1 is essential for normal fly development and loss of dRif1 impairs temporal regulation of initiation of DNA replication. In multiple tissues dRif1 colocalizes with HP1, a protein known to orchestrate timing of replication in fly. dRif1 associates with chromosomes in a mitotic stage-dependent manner coinciding with dephosphorylation of histones. Ectopic expression of dRif1 causes enlarged larval imaginal discs and early pupal lethality which is completely reversed by co-expression of PP1 87B, the major protein phosphatase in Drosophila, indicating genetic and functional interaction. These findings suggest that dRif1 is an adaptor for PP1 and functions by recruiting PP1 to multiple sites on the chromosome.
authors.affiliation: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad- 500 046, INDIA.
authors.forename: Easwaran
authors.initials: E
authors.lastname: Sreesankar
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal road, Hyderabad-500 007, INDIA.
authors.forename: Vellaichamy
authors.initials: V
authors.lastname: Bharathi
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal road, Hyderabad-500 007, INDIA.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Mishra
authors.affiliation: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad- 500 046, INDIA.
authors.forename: Krishnaveni
authors.initials: K
authors.lastname: Mishra
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D004330:Drosophila / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000096:biosynthesis / Q000235:genetics*; D016615:Telomere / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; C000606084:Rif1 protein, Drosophila; D034501:Telomere-Binding Proteins; C452193:heterochromatin protein 1, Drosophila; D054645:Protein Phosphatase 1