Artesunate, the active agent from Artemisia annua L. used in the traditional Chinese medicine, is being applied as a first-line drug for malaria treatment, and trials are ongoing that include this drug in cancer therapy. Despite increasing interest in its therapeutic application, the mode of cell killing provoked by artesunate in human cells is unknown. Here, we show that artesunate is a powerf...

Eukaryotes have evolved complex mechanisms to repair DNA double-strand breaks (DSBs) through coordinated actions of protein sensors, transducers, and effectors. Here we show that ∼21-nucleotide small RNAs are produced from the sequences in the vicinity of DSB sites in Arabidopsis and in human cells. We refer to these as diRNAs for DSB-induced small RNAs. In Arabidopsis, the biogenesis of diRNAs...

—The DNA damage response (DDR) mechanisms represent a vital line of defense against exogenous and endogenous DNA damage to enhance two distinct outcomes, survival and the maintenance of genomic stability. The latter is critical for cancer avoidance. DDR processes encompass repair pathways and signal transduction mechanisms that activate cell cycle checkpoint arrest and apoptosis. DNA double str...

Intercalator-induced DNA strand breaks in mammalian cells represent topoisomerase II:DNA complexes trapped by intercalators. These complexes are detected as protein-associated DNA single-strand breaks (SSB) and DNA double-strand breaks (DSB) by filter elution. Using Chinese hamster lung fibroblasts (V79 cells) that were treated for 30 min with various concentrations of 4'-(9-acridinylamino)meth...

DNA repair activity of malignant cells seems to influence therapeutic outcome and patients' survival. Herein, we investigated the mechanistic basis for the link between DNA repair efficiency and response to antimyeloma therapy. Nucleotide excision repair (NER), interstrand cross-links repair (ICL/R), double-strand breaks repair (DSB/R), and chromatin structure were evaluated in multiple myeloma...

The product of the Brca1 tumor-suppressor gene is involved in multiple aspects of the cellular DNA damage response (DDR), including activation of cell-cycle arrests and DNA double-stranded break (DSB) repair by homologous recombination. Prior reports demonstrated that BRCA1 recruitment to areas of DNA breakage depended on RAP80 and the RNF8/ RNF168 E3 ubiquitin ligases. Here, we extend these fi...

Double-strand breaks (DSBs) are lethal DNA lesions, which are repaired by homologous recombination in Escherichia coli To study DSB processing in vivo, we induced DSBs into the E. coli chromosome by γ-irradiation and measured chromosomal degradation. We show that the DNA degradation is regulated by RecA protein concentration and its rate of association with single-stranded DNA (ssDNA). RecA dec...

A DNA double-strand break (DSB) is the most severe form of DNA damage and is mainly repaired through homologous recombination (HR), which has a high fidelity, or non-homologous end joining (NHEJ), which is prone to errors. Defects in the DNA damage response lead to genomic instability and ultimately the predisposition of organs to cancer. Protein inhibitor of activated STAT-1 (PIAS1), which is ...

The activities of many DNA-repair proteins are controlled through reversible covalent modification by ubiquitin and ubiquitin-like molecules. Nonhomologous end-joining (NHEJ) is the predominant DNA double-strand break (DSB) repair pathway in mammalian cells and is initiated by DSB ends being recognized by the Ku70/Ku80 (Ku) heterodimer. By using MLN4924, an anti-cancer drug in clinical trials t...

During the DNA damage response (DDR), ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, is involved in the elimination of the ubiquitin signal from damaged sites and is...