Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth of budding yeast, Saccharomyces cerevisiae, was inhibited in medium containing 25 microM farnesol (FOH). The FOH-treated cells were still viable, and were characterized by a transition from budded to unbudded phase as well as a significant loss of intracellular diacylglycerol (DAG). FOH-induced growth inhibition could be effectively prevented by the coaddition of a membrane-permeable DAG analogue which can activate yeast protein kinase C (PKC). However, yeast cell growth was not initiated upon addition of the PKC activator when the cells had been pretreated with FOH for 20 min. The failure in cell growth recovery was believed to be due to a signalling-mediated cell cycle arrest in FOH-pretreated cells. Differential display analysis demonstrated that the expression of cell cycle genes encoding DNA ligase (CDC9) and histone acetyltransferase (HAT2) was strongly repressed in FOH-treated cells. Repression of the expression of these genes was effectively cancelled when cells were grown in medium supplemented with DAG. The authors propose an interference with a phosphatidylinositol-type signalling which is involved in cell cycle progression as a cause of FOH-induced growth inhibition in yeast cells.
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PMID:Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism. 1007 11

The Saccharomyces cerevisiae SPT10 protein possesses a DNA-binding domain that is fused to a putative histone acetyltransferase domain. It binds specifically to upstream-activating sequence elements in the core histone promoters and plays a direct role in histone gene regulation. SPT10 is also required for cell-cycle-specific K56 acetylation at histone genes, allowing the recruitment of the nucleosome remodeling factor Snf5 and subsequent regulation of gene transcription. We reisolated the SPT10 gene in a functional genome-wide screen designed to identify haploid yeast mutants that are hypersensitive to the antitumor drug bleomycin, which acts by damaging DNA. In addition to bleomycin, we show that spt10Delta mutants are also hypersensitive to a limited set of genotoxic agents that create DNA strand breaks, but not to 254-nm ultraviolet light or 4-nitroquinoline-1-oxide, which generate helix distortion. The hypersensitivities of the spt10Delta mutant to the genotoxic agents are rescued by a single copy plasmid carrying the SPT10 gene. We further showed that spt10Delta mutants displayed a modest twofold increase spontaneous mutant frequency, as compared to the parent. Following exposure to bleomycin, these mutants accumulate unrepaired lesions, e.g., DNA strand breaks with blocked 3'-ends in the chromosomal DNA. This defect is not due to the altered expression level or the enzymatic activities of a key DNA repair enzyme, APN1, which is known to repair DNA strand breaks with blocked ends. We propose that SPT10 mediates repair of a subset of DNA lesions by acetylating histones to promote recruitment of DNA repair enzymes.
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PMID:Deletion of the chromatin remodeling gene SPT10 sensitizes yeast cells to a subclass of DNA-damaging agents. 1707 97