A genome-wide deletion mutant screen identifies pathways affected by nickel sulfate in Saccharomyces cerevisiae.

Background: The understanding of the biological function, regulation, and cellular interactions of the yeast genome and proteome, along with the high conservation in gene function found between yeast genes and their human homologues, has allowed for Saccharomyces cerevisiae to be used as a model organism to deduce biological processes in human cells. Here, we have completed a systematic screen of the entire set of 4,733 haploid S. cerevisiae gene deletion strains (the entire set of nonessential genes for this organism) to identify gene products that modulate cellular toxicity to nickel sulfate (NiSO(4)).

A genome-wide screen in Saccharomyces cerevisiae reveals pathways affected by arsenic toxicity.

We have used Saccharomyces cerevisiae to identify toxicologically important proteins and pathways involved in arsenic-induced toxicity and carcinogenicity in humans. We performed a systemic screen of the complete set of 4733 haploid S. cerevisiae single-gene-deletion mutants to identify those that have decreased or increased growth, relative to wild type, after exposure to sodium arsenite (NaAsO(2)).

Heterochromatinization as a potential mechanism of nickel-induced carcinogenesis.

Epigenetics refers to heritable patterns of gene expression that do not depend on alterations of the genomic DNA sequence. Nickel compounds have demonstrated carcinogenicity without any associated mutagenesis, suggesting that its mechanism of carcinogenesis is epigenetic in nature. One such potential mechanism is the heterochromatinization of chromatin within a region of the genome containing a gene sequence, inhibiting any further molecular interactions with that underlying gene sequence and effectively inactivating that gene.

Nickel compounds induce phosphorylation of histone H3 at serine 10 by activating JNK-MAPK pathway.

Nickel (Ni) is a known carcinogen, although the mechanism of its carcinogenicity is not clear. Here, we provide evidence that Ni can induce phosphorylation of histone H3 at its serine 10 residue in a c-jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK)-dependent manner. Ni induces the phosphorylation of JNK, with no effect on the phosphorylation states of the extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinases.

Arsenite alters global histone H3 methylation.

Arsenic (As) is a well-characterized human carcinogen but is generally not mutagenic. The evidence that As induces both loss of global DNA methylation and gene promoter DNA hypermethylation has suggested that epigenetic mechanisms may play an important role in As-induced carcinogenesis. In the present study, we examined the change in histone methylation by As exposure.

Nickel compounds induce histone ubiquitination by inhibiting histone deubiquitinating enzyme activity.

Nickel (Ni) compounds are known carcinogens but underlying mechanisms are not clear. Epigenetic changes are likely to play an important role in nickel ion carcinogenesis. Previous studies have shown epigenetic effects of nickel ions, including the loss of histone acetylation and a pronounced increase in dimethylated H3K9 in nickel-exposed cells.

NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states.

N-myc downstream-regulated gene 1 (NDRG1) is an intracellular protein that is induced under a wide variety of stress and cell growth-regulatory conditions. NDRG1 is up-regulated by cell differentiation signals in various cancer cell lines and suppresses tumor metastasis. Despite its specific role in the molecular cause of Charcot-Marie-Tooth type 4D disease, there has been more interest in the gene as a marker of tumor progression and enhancer of cellular differentiation.

Linker histone interaction shows divalent character with both supercoiled and linear DNA.

The interaction of linker histone H1 with both linear and superhelical double-stranded DNA has been investigated at low ionic strengths. Gel mobility retardation experiments demonstrate strikingly different behavior for the two forms of DNA. First, the experiments strongly suggest that linker histone binds to superhelical DNA in a negatively cooperative mode.