Ricerc@Sapienza

In eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B-6 salvage pathway to produce pyridoxal 5'-phosphate (PLP), the active form of the vitamin, which is implicated in numerous crucial metabolic reactions. In Drosophila, mutations in the dPdxk gene cause chromosome aberrations (CABs) and increase glucose content in larval hemolymph. Both phenotypes are rescued by the expression of the wild type human PDXK counterpart.

Trimethylguanosine synthase 1 (TGS1) is a conserved enzyme that mediates formation of the trimethylguanosine cap on several RNAs, including snRNAs and telomerase RNA. Previous studies have shown that TGS1 binds the Survival Motor Neuron (SMN) protein, whose deficiency causes spinal muscular atrophy (SMA). Here, we analyzed the roles of the Drosophila orthologs of the human TGS1 and SMN genes.

Pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, works as cofactor in numerous enzymatic reactions and it behaves as antioxidant molecule. PLP deficiency has been associated to many human pathologies including cancer and diabetes and the mechanism behind this connection is now becoming clearer. Inadequate intake of this vitamin increases the risk of many cancers; furthermore, PLP deprivation impairs insulin secretion in rats, whereas PLP supplementation prevents diabetic complications and improves gestational diabetes.

Pyridoxine/pyridoxamine 5′‐phosphate oxidase (PNPO) and pyridoxal kinase (PDXK)
cooperate to produce pyridoxal 5′‐phosphate (PLP), the active form of vitamin B6. PDXK
phosphorylates pyridoxine, pyridoxamine, and pyridoxal by producing PNP, PMP, and PLP,
whereas PNPO oxidizes PNP, PMP, into PLP. We previously demonstrated that PDXK
depletion in Drosophila and human cells impacts on glucose metabolism and DNA integrity.
Here we characterized sgll, the Drosophila ortholog of PNPO gene, showing that its silencing

Aurora-A is a conserved mitotic kinase overexpressed in many types of cancer. Growing evidence shows that Aurora-A plays a
crucial role in DNA damage response (DDR) although this aspect has been less characterized. We isolated a new aur-A mutation, named aur-A949, inDrosophila, and we showed that it causes chromosome aberrations (CABs). In addition, aur-A

Morgana/CHORDC1/CHP1 is a highly conserved CHORD (Cysteine and Histidine Rich Domain) containing protein that has been proposed to function as an Hsp90 cochaperone. Morgana deregulation promotes carcinogenesis in both mice and humans while, in Drosophila, loss of morgana (mora) causes lethality and a complex mitotic phenotype that is rescued by a human morgana transgene. Here, we show that Drosophila Morgana localizes to mitotic spindles and co-purifies with the Hsp90- R2TP-TTT super-complex, and with additional well-known Hsp90 co-chaperones.

The Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. Acetyl-CoA is a high-energy intermediate common to a large number of metabolic processes including protein acetylation reactions. This renders ACL a key regulator of histone acetylation levels and gene expression in diverse organisms including humans.

Heterochromatin Protein 1 (HP1) and the Mre11-Rad50-Nbs1 (MRN) complex are conserved factors that play crucial role in genome stability and integrity. Despite their involvement in overlapping cellular functions, ranging from chromatin organization, telomere maintenance to DNA replication and repair, a tight functional relationship between HP1 and the MRN complex has never been elucidated. Here we show that the Drosophila HP1a protein binds to the MRN complex through its chromoshadow domain (CSD).

The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones.

Several studies have shown that RNAi-mediated depletion of splicing factors (SFs) results in mitotic abnormalities. However, it is currently unclear whether these abnormalities reflect defective splicing of specific pre-mRNAs or a direct role of the SFs in mitosis. Here, we show that two highly conserved SFs, Sf3A2 and Prp31, are required for chromosome segregation in both Drosophila and human cells. Injections of anti-Sf3A2 and anti-Prp31 antibodies into Drosophila embryos disrupt mitotic division within 1 min, arguing strongly against a splicing-related mitotic function of these factors.