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...

Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present st...

Subject codes: [134] Pathophysiology [137]Cell biology/structural biology [96] Mechanism of atherosclerosis/growth factors [162] Smooth muscle proliferation ABSTRACT Rationale: DNA damage and the DNA damage response (DDR) have been identified in human atherosclerosis, including in vascular smooth muscle cells (VSMCs). However, although double strand breaks (DSBs) are hypothesized to promote pla...

The antitumor drug Etoposide (ETO) induces DNA double-strand breaks (DSB) and is associated with the development of secondary neoplasms in treated patients. DSB are repaired by two main mechanisms, homologous recombination (HR) classical non-homologous end joining (c-NHEJ). When HR c-NHEJ defective, PARP-1-dependent alternative end-joining (alt-EJ) pathway. involvement alt-EJ progression induce...

Genomic integrity is of outmost importance for the survival at the cellular and the organismal level and key to human health. To ensure the integrity of their DNA, cells have evolved maintenance programs collectively known as the DNA damage response. Particularly challenging for genome integrity are DNA double-strand breaks (DSB) and defects in their repair are often associated with human disea...

Failure to repair DNA double strand breaks (DSB) can lead to chromosomal rearrangements and eventually to cancer or cell death. Radiation and environmental pollutants induce DSB and this is of particular relevance to plants due to their sessile life style. DSB also occur naturally in cells during DNA replication and programmed induction of DSB initiates the meiotic recombination essential for g...

DNA repair pathways are crucial for the maintenance of genome integrity. The pathway that repairs DNA double-strand breaks (DSB) has components involved in both signaling and repairing DNA damage. Impairing DSB repair using specific inhibitors of signaling or repair might, in principle, sensitize tumor cells to particular DNA-damaging agents. Moreover, the existence of specific defects in DNA r...

DNA double-strand breaks (DSB) are created by ionizing radiation, an important environmental genotoxic agent. DSB are repaired by two mechanisms associated with recombination. In eukaryotic cells homologous recombination depends on genes belonging to the RAD52 epistatic group. Alternative pathway, DNA end-joining in non-homologous recombination involves DNA-dependent protein kinase (DNA-PK).

The E3 ubiquitin ligases ring finger protein (RNF) 8 and RNF168 transduce the DNA double-strand break (DSB) response (DDR) signal by ubiquitinating DSB sites. The depletion of RNF8 or RNF168 suppresses the accumulation of DNA-repair regulating factors such as 53BP1 and RAP80 at DSB sites, suggesting roles for RNF8- and RNF168-mediated ubiquitination in DSB repair. This mini-review provides a br...