ABSTRACT
The putative eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for cell viability and the only cellular protein known to contain the unusual amino acid residue hypusine. eIF5A has been implicated in translation initiation, cell proliferation, nucleocytoplasmic transport, mRNA decay, and actin polarization, but the precise biological function of this protein is not clear. However, eIF5A was recently shown to be directly involved with the translational machinery. A screen for synthetic lethal mutations was carried out with one of the temperature-sensitive alleles of TIF51A (tif51A-3) to identify factors that functionally interact with eIF5A and revealed the essential gene YPT1. This gene encodes a small GTPase, a member of the rab family involved with secretion, acting in the vesicular trafficking between endoplasmatic reticulum and the Golgi. Thus, the synthetic lethality between TIF51A and YPT1 may reveal the connection between translation and the polarized distribution of membrane components, suggesting that these proteins work together in the cell to guarantee proper protein synthesis and secretion necessary for correct bud formation during G1/S transition. Future studies will investigate the functional interaction between eIF5A and Ypt1 in order to clarify this involvement of eIF5A with vesicular trafficking.
Subject(s)
Genes, Lethal/genetics , Mutation/genetics , Peptide Initiation Factors/genetics , RNA-Binding Proteins/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , rab GTP-Binding Proteins/genetics , G1 Phase/genetics , S Phase/genetics , Saccharomyces cerevisiae/cytology , Transport Vesicles/geneticsABSTRACT
Hydroxyurea is considered an antineoplastic drug, which also plays an important role in the treatment of sickle cell anemia patients. We evaluated and compared the clastogenic and cytotoxic effects of hydroxyurea, using chromosomal aberrations and mitotic index, respectively, as endpoints. In vitro short-term cultures of lymphocytes were exposed to several concentrations of this drug, at various cell cycle phases. There was a significant increase in the cytotoxicity of hydroxyurea at G1 and G1/S as well in the G2 phase of the cell cycle. Hydroxyurea did not significantly increase chromosome aberrations. There was an S-dependent cytotoxic effect of hydroxyurea, which is expected based on the known activity of hydroxyurea as an inhibitor of ribonucleotide reductase
Subject(s)
Humans , Chromosome Aberrations/chemically induced , Antineoplastic Agents/toxicity , Hydroxyurea/toxicity , Interphase/drug effects , Lymphocytes/drug effects , Analysis of Variance , Endpoint Determination , G1 Phase/drug effects , G1 Phase/genetics , /drug effects , /genetics , S Phase/drug effects , S Phase/genetics , Interphase/genetics , Mitotic Index , Mutagenicity Tests/methodsABSTRACT
We studied the DNA content, DNA index and cell cycle parameters that are reliable markers for assessing the proliferative activity and aggressiveness of malignancies. Cytometric DNA analysis was performed on formalin-fixed paraffin embedded sections from 36 Iraqi patients with oral squamous cell carcinoma. The results showed that 20 of 36 cases [55.5%] were diploid, while 15 cases [41.7%] were aneuploid. Significantly higher S-phase fractions and higher DNA indices characterized aneuploid tumours. Nuclear DNA analysis as part of the evaluation of oral squamous cell carcinoma will influence the selection of appropriate treatment strategies
Subject(s)
Adolescent , Adult , Aged, 80 and over , Female , Humans , Male , Middle Aged , Aneuploidy , Case-Control Studies , DNA, Neoplasm/analysis , Diploidy , Flow Cytometry/methods , Lymphatic Metastasis/pathology , Mouth Neoplasms/pathology , Prognosis , S Phase/geneticsABSTRACT
A genetic approach was adopted to analyze the cell cycle G(O)(G (1) (S transition in mouse Balb/ 3T3 fibroblasts (clone A3l). We designed selection procedures to isolate revertant from the EJ-ras transformed Balb/3T3 ribroblasts that had recovered strict -control of the G(O) ( G(1), transition by serum growth factors. The aim was to uncover phenotypic traits associated with malignancy (high growth rate G(1) phase shortening and high tumorigenicity) that segregate independently.