Phosphorylation of H2AX on Ser139 (γH2AX) after exposure to ionizing radiation produces nuclear foci that are detectable by immunofluorescence microscopy. These so-called γH2AX foci have been adopted as quantitative markers for DNA double-strand breaks. High numbers of spontaneous γH2AX foci have also been reported for some human solid tumor-derived cell lines, but the molecular mechanism(s) fo...

Replication foci are generated by many viruses to concentrate and localize viral DNA synthesis to specific regions of the cell. Expression of the HPV16 E1 and E2 replication proteins in keratinocytes results in nuclear foci that recruit proteins associated with the host DNA damage response. We show that the Brd4 protein localizes to these foci and is essential for their formation. However, when...

The role of c-myc in prostatic carcinogenesis is poorly understood. The pathogenetic relationship between high-grade prostatic intraepithelial neoplasia (PIN), prostatic carcinoma, and metastases is not well-defined. We used fluorescence in situ hybridization (FISH) with a region-specific probe for c-myc (band 8q24) and chromosome enumeration probes for chromosomes 7, 8, 10, 12, and Y to evalua...

Cyclin E/Cdk2 is necessary for replication-dependent histone mRNA biosynthesis, but how it controls this process in early development is unknown. We show that in Drosophila embryos the MPM-2 monoclonal antibody, raised against a phosphoepitope from human mitotic cells, detects Cyclin E/Cdk2-dependent nuclear foci that colocalize with nascent histone transcripts. These foci are coincident with t...

The membrane-bound transcription factor ATF6α is activated by proteolysis during endoplasmic reticulum (ER) stress. ATF6α target genes encode foldases, chaperones, and lipid biosynthesis enzymes that increase protein-folding capacity in response to demand. The off-state of ATF6α is maintained by its spatial separation in the ER from Golgi-resident proteases that activate it. ER stress induces t...

The immunological synapse formed during mature T cell activation consists of a central cluster of TCR and MHC molecules surrounded by a ring of LFA-1 and ICAM-1. We examined synapse formation in thymocytes undergoing activation in a lipid bilayer system by following the movement of fluorescent MHC and ICAM-1 molecules. Immature CD4(+)CD8(+) thymocytes formed a decentralized synapse with multipl...

In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examin...

The bioequilibrium of antioxidant and prooxidant has a crucial role in cellular function with free radical defense (Valko et al., 2006). Oxidative stress is defined by the excess of free radicals and antioxidant depletion. It was implicated on biomolecules such as protein, lipid, and nucleic acid (Sies, 1997; Finkel & Holbrook, 2000). Cellular oxidative stress eventually caused tissue injury an...

A case of ovarian clear cell adenofibroma of borderline malignancy in a 59-year-old woman is presented with histochemical and electron microscopic observation. The tumor was histologically composed of tubular component lined in part with flat or cuboidal clear as well as hobnail cells with mild cytologic atypia and abundant stromal component containing foci of calcification. The epithelial cell...

Immunofluorescence detection of gammaH2AX foci is a widely used tool to quantify the induction and repair of DNA double-strand breaks (DSBs) induced by ionising radiation. We observed that X-irradiation of mammalian cells exposed on glass slides induced twofold higher foci numbers compared to irradiation with gamma-rays. Here, we show that the excess gammaH2AX foci after X-irradiation are produ...