Different organisms display widely different numbers of the programmed double-strand breaks (DSBs) that initiate meiotic recombination (e.g., hundreds per meiocyte in mice and humans vs. dozens in nematodes), but little is known about what drives these species-specific DSB set points or the regulatory pathways that control them. Here we examine male mice with a lowered dosage of SPO11, the meio...

Friedreich ataxia is caused by an expanded (GAA*TTC)n sequence, which is unstable during intergenerational transmission and in most patient tissues, where it frequently undergoes large deletions. We investigated the effect of DSB repair on instability of the (GAA*TTC)n sequence. Linear plasmids were transformed into Escherichia coli so that each colony represented an individual DSB repair event...

In this study, the effect of DNA single strand breaks (ssb) on the neutral (pH 9.6) filter elution of DNA from Chinese hamster ovary (CHO K1) cells containing DNA double strand breaks (dsb) was investigated. Protein associated ssb were induced by the inhibition of DNA topoisomerase I with camptothecin (cpt). Protein associated dsb were introduced by treating cells with the DNA topoisomerase II ...

Despite the effectiveness of currently available human immunodeficiency virus type 1 (HIV-1) therapies, a continuing need exists for new drugs to treat HIV-1 infection. We investigated the mechanism by which 3-O-[3',3'-dimethylsuccinyl]-betulinic acid (DSB) inhibits HIV-1 replication. DSB functions at a late stage of the virus life cycle but does not inhibit the HIV-1 protease in vitro or inter...

Introduction: A high risk for development of severe side effects after radiotherapy may be correlated with high cellular radiosensitivity. To enhance radiation therapy efficiency a fast and reliable in-vitro test is desirable to identify radiosensitive patients. The aim of present study was to identify the mechanism of radiation induced DNA double-strand breaks (DSBs) and DSB r...

BACKGROUND Understanding suicidal behavior is an important component of assessing suicidality in psychiatric patients. GlaxoSmithKline (GSK) conducted a meta-analysis of randomized, placebo-controlled trials to compare suicidality in adult patients treated with paroxetine vs. placebo. The goal was to identify emergent clinical characteristics of patients with definitive suicidal behavior (DSB: ...

background: immunotoxins are comprised of both the cell targeting and the cell killing moieties. we previously established a new immunotoxin, i.e. shiga toxin granulocyte macrophage-colony stimulating factor (stxa1-gm-csf), comprises of catalytic domain of stx, as a killing moiety and gm-csf, as a cell targeting moiety. in this study, the ability of the immunotoxin to induce apoptosis and doubl...

Differences in ex vivo cell culture conditions can drastically affect stem cell physiology. We sought to establish an assay for measuring the effects of chemical, environmental, and genetic manipulations on the precision of repair at a single DNA double-strand break (DSB) in pluripotent and somatic human cells. DSBs in mammalian cells are primarily repaired by either homologous recombination (H...

Fibroblasts from patients with the severe laminopathy diseases, restrictive dermopathy (RD) and Hutchinson Gilford progeria syndrome (HGPS), are characterized by poor growth in culture, the presence of abnormally shaped nuclei and the accumulation of DNA double-strand breaks (DSB). Here we show that the accumulation of DSB and poor growth of the fibroblasts but not the presence of abnormally sh...

Wortmannin, an inhibitor of p110 PI 3-kinase, also inhibits DNA-dependent protein kinase, which is known to mediate DNA double strand break repair. It was recently demonstrated that wortmannin sensitized cells to ionizing radiation (IR) (Price and Youmell, Cancer Res., 56, 246-250, 1996). Wortmannin was used to determine if the potentiation of IR-induced cytotoxicity in Chinese hamster ovary ce...