introduction h istone deacetylase inhibitors (hdis), as  radiation sensitizing agents, are considered as a novel class of anti-cancer factors, which are studied in various tumor cell-lines. valproic acid (vpa) is an hdi, which is effectively used in the treatment of epilepsy, migraines, and some particular types of depression. in this study, we evaluated the effects of vpa and ionizing radiatio...

Ubiquitination plays an important role in the DNA damage response. We identified a novel interaction of the E3 ubiquitin ligase RNF8 with Nbs1, a key regulator of DNA double-strand break (DSB) repair. We found that Nbs1 is ubiquitinated both before and after DNA damage and is a direct ubiquitination substrate of RNF8. We also identified key residues on Nbs1 that are ubiquitinated by RNF8. By us...

Prabha Balaram1,*, Smriti M Krishna1, Susan James2, Vino. T. Cheriyan1, Sreelekha Therakathinal Thankappan1, Aleyamma Mathew3 Division of Cancer Research, Regional Cancer Centre, Medical College. P.O, Trivandrum 695 011, Kerala, India. Department of ENT, Medical College, Trivandrum 695-011, Kerala, India Department of Statistics, Regional Cancer Centre, Trivandrum, Kerala, India _______________...

A broken DNA molecule is difficult to repair, highly mutagenic, and extremely cytotoxic. Such breaks can be repaired by homology-independent or homology-directed mechanisms. Little is known about the network that controls the repair pathway choice except that a licensing step for homology-mediated repair exists, called DNA-end resection. The choice between these two repair pathways is a key eve...

The analysis of double-strand break (DSB) repair is complicated by the existence of several pathways utilizing a large number of genes. Moreover, many of these genes have been shown to have multiple roles in DSB repair. To address this complexity we used a repair reporter construct designed to measure multiple repair outcomes simultaneously. This approach provides estimates of the relative usag...

Experiments with the supF20 mutagenesis system demonstrate that extracts from Bloom's syndrome (BS) cells are unable to use microhomology elements within the supF20 gene to restore supF function after the induction of a double-strand break (DSB). Additional experiments with the pUC18 mutagenesis system demonstrate that although the efficiency and fidelity of DSB repair by BS extracts are compar...

DNA double-strand breaks (DSBs) are the most dangerous form of DNA damage and can lead to death, mutation, or malignant transformation. Mammalian cells use three major pathways to repair DSBs: homologous recombination (HR), classical nonhomologous end joining (C-NHEJ), and alternative end joining (A-NHEJ). Cells choose among the pathways by interactions of the pathways with CtIP and 53BP1. HR i...

The neutral filter elution method and the neutral comet assay have been used to analyze radiation-induced DNA damage and repair in 6 human tumor cell lines: HT-144 melanoma; DU-145 prostate carcinoma; U-87 glioma; WiDr and HT-29 colon adenocarcinomas; and SiHa cervical carcinoma. In spite of large differences in intrinsic radiosensitivity measured using a clonogenic assay, double-strand break i...

Targeted DNA double-strand breaks have been shown to significantly increase the frequency and precision of genome editing. In the past two decades, several double-strand break technologies have been developed. CRISPR-Cas9 has quickly become the technology of choice for genome editing due to its simplicity, efficiency and versatility. Currently, genome editing in plants primarily relies on deliv...

The radiosensitive mutant xrs-6, derived from Chinese hamster ovary cell line CHO-K1, has been demonstrated to be defective in DNA double-strand break repair and also in its proficiency to undergo V(D)J recombination. Recent work has provided both genetic and biochemical evidence that the M(r) 80,000 subunit of the Ku protein is able to complement the radiosensitivity and the V(D)J recombinatio...