The D. melanogaster mei-41 gene is required for DNA repair, mitotic chromosome stability, and normal levels of meiotic recombination in oocytes. Here we show that the predicted mei-41 protein is similar in sequence to the ATM (ataxia telangiectasia) protein from humans and to the yeast rad3 and Mec1p proteins. There is also extensive functional overlap between mei-41 and ATM. Like ATM-deficient cells, mei-41 cells are exquisitely sensitive to ionizing radiation and display high levels of mitotic chromosome instability. We also demonstrate that mei-41 cells, like ATM-deficient cells, fail to show an irradiation-induced delay in the entry into mitosis that is characteristic of normal cells. Thus, the mei-41 gene of Drosophila may be considered to be a functional homolog of the human ATM gene.

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Following our investigations on food additive production through fermentation, we studied properties of red pigments secreted by Monascus ruber in submerged culture, using ethanol and glutamate as carbon and nitrogen sources. After extraction and purification, these colorants were suspended in water for evaluation. The stability of the extract was tested both in solution and when incorporated into meat products (sausage and plte). The pigments added to sausage or pate remained stable when stored for 3 mo at 4°C; their stability was between 92 and 98%. Sensory tests revealed that Monascus pigments could replace some traditional food additives such as nitrite salts or cochineal.

A chemically defined medium with glutamic acid as nitrogen source was devised for the culture of two species of Monascus (M. ruber and M. purpurercr), resulting in optimum production of their pigments and their chemical structures (both free and complexed) were compared. Structural data on two major complex pigments in aqueous solution were obtained by IR, UV, NMR and MS. They were free pigments linked to glutamic acid by amino groups, where nitrogen replaced the pyronoid oxygen.

We have isolated an Arabidopsis talana cDNA that complements the methyl me efonate-sensltive phenotype of an Escherichia coi double mutant deficient in 3-methyladenine glycosylases (DNA-3-methyladenine glycosidases I and U, EC 3.2.2.20 and 3.2.2.21, respectively, encoded by tag and alkA). ExpressionoftheArabidopsis cDNA enhanes the methyl meh on resistance of the E. coil double mutant by nearly four orders of magnitude. The cDNA corresponds to a single-copy, nely encoded sequence which specifies a predicted 28.1-kDa protein with a charge of +8 at pH 7.0. Enzymatic analysis of extracts prepared from the tnormed mutants indctes that the cDNA encodes a 3-methyladenine glycosylase. The predicted amino acid sequence of the Arabidopsis glycosylase ha significant homology to other eukaryotic 3-methyladenine glycosylases.All living things are subject to DNA damage in a wide variety of forms. Environmental and man-made toxins such as UV light, chemical mutagens, fungal and bacterial toxins, and ionizing radiation result in the formation of cross-links, single-and double-stranded breaks, and chemical adducts in DNA. In addition, because the genome is located in a chemically reactive environment, some amount of DNA damage occurs as an inevitable result of the interaction of nucleic acids with cellular alkylating and oxidizing agents. These modified bases can, in the absence of repair, contribute substantially to the cell's spontaneous mutation rate (1-4). DNA repair mechanisms, which protect the cell from the cytotoxic and mutagenic effects of these lesions, have been demonstrated in a variety of organisms, from bacteriophage to humans. The various pathways for repair include both nucleotide excision repair mechanisms, which repair a broad spectrum of lesions, and more specialized base repair enzymes (largely, though not exclusively, glycosylases).The study of DNA repair, recombination, and replication in plants has lagged far behind the study of these processes in microbial and mammalian systems. Molecular isolation of the genes involved in DNA enzymology in higher plants has been limited to a handful of clones. These include two genes cloned by taking advantage of homologous nucleotide sequences: the Arabidopsis gene for topoisomerase 1 (5) and an apparent homolog of the Escherichia coli recA gene, localized to the chloroplasts, from Arabidopsis and Pisum sativum (6). Hays and coworkers (41, 42) have isolated several Arabidopsis clones on the basis of their ability to partially complement the UV-sensitive phenotype of an E. coli recA-, phr-, uvrC-triple mutant. With the exception of the TOP] clone, the biochemical activities encoded by these cDNAshave not yet been identified.

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Estrogens are oncogenic hormones at a high level in breast, prostate, endometrial and lung cancer. Estrogens are synthesized by aromatase which has been used as a biomarker both in breast and lung cancer. Estrogen biological activities are executed by their classic receptors (ERα and ERβ). ERα has been described as a cancer promoter and ERβ, as a possible tumor suppressor. Both receptors are present at low levels in primary multiforme glioblastoma (GBM). The GBM frequency is 50 % higher in men than in women. The GBM patient survival period ranges from 7 to 18 months. The purpose of this pilot study was to evaluate aromatase and estrogen receptor expression, as well as 17ß-estradiol concentration in astrocytoma patients biopsies to obtain a prognosis biomarker for these patients. We analyzed 36 biopsies of astrocytoma patients with a different grade (I-IV) of malignity. Aromatase and estrogen receptor mRNA expression were analyzed by semiquantitative RT-PCR, and the E2 levels, by ELISA. E2 concentration was higher in GBM, compared to grade II or III astrocytomas. The number of cells immunoreactive to aromatase and estrogen receptors decreased as the grade of tumor malignity increased. Aromatase mRNA expression was present in all biopsies, regardless of malignity grade or patient age or gender. The highest expression of aromatase mRNA in GBM patients was associated to the worst survival prognostic (6.28 months). In contrast lowest expression of ERα mRNA in astrocytoma patients had a worst prognosis. In conclusion, aromatase and ERα expression could be used as prognosis biomarkers for astrocytoma patients.