Recent crystallographic studies of DNA-repair enzymes have provided the structural basis for the recognition of damaged DNA. The results imply that flipping out of the base is a common and crucial event in DNA repair. Two classes of repair enzymes that recognize distinct types of damage may exist. DNA-repair enzymes that share similar folds and DNA binding motifs have been proposed to belong to...

The uvrD252 mutation leads to increased UV sensitivity, diminished dimer excision and host cell reactivation capacity, and an increase in the average patch size after repair replication. A recA56 uvrD252 double mutant was far more resistant to UV than was a recA56 uvrB5 double mutant. Its host cell reactivation capacity was identical to that of uvrD252 single mutant and was far greater than tha...

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a encoded by the PRKDC gene in humans and plays crucial role repairing DNA double-strand breaks (DSBs). Recent studies have revealed that DNA-PKcs has additional functions cell beyond DSB repair, including transcriptional regulation, telomere protection capping, preserving chromosomal integrity, regulating senescence, apoptosis, a...

Proinflammatory cytokines induce nitric oxide-dependent DNA damage and ultimately -cell death. Not only does nitric oxide cause -cell damage, it also activates a functional repair process. In this study, the mechanisms activated by nitric oxide that facilitate the repair of damaged -cell DNA are examined. JNK plays a central regulatory role because inhibition of this kinase attenuates the repai...

Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxi...

Camptothecin (CPT) and its analogues are chemotherapeutic agents that covalently and reversibly link DNA Topoisomerase I to its nicked DNA intermediate eliciting the formation of DNA double strand breaks (DSB) during replication. The repair of these DSB involves multiple DNA damage response and repair proteins. Here we demonstrate that CPT-induced DNA damage promotes functional interactions bet...

DNA repair safeguards the genome against a diversity of DNA damaging agents. Although the mechanisms of many repair proteins have been examined separately in vitro, far less is known about the coordinated function of the whole repair machinery in vivo. Furthermore, single-cell studies indicate that DNA damage responses generate substantial variation in repair activities across cells. This revie...

The major actions of nucleoside analogs such as arabinosylcytosine (ara-C) and fludarabine occurs after their incorporation into DNA, during either replication or repair synthesis. The metabolic salvage and DNA incorporation of the normal nucleoside, deoxycytidine, is functionally compartmentalized toward repair synthesis in a process regulated by ribonucleotide reductase. The aim of this study...

PURPOSE Fibroblast growth factor 2 (FGF2) is a well-known survival factor. However, its role in DNA repair is poorly documented. The present study was designed to investigate in epidermoid carcinoma cells the potential role of FGF2 in DNA repair. MATERIALS AND METHODS The side population (SP) with cancer stem cell-like properties and the main population (MP) were isolated from human A431 squa...

The development of resistances to conventional anticancer drugs compromises the efficacy of cancer treatments. In the case of DNA-targeting chemotherapeutic agents, cancer cells may display tolerance to the drug-induced DNA lesions and/or enhanced DNA repair. However, the role of DNA damage response (DDR) and DNA repair in this chemoresistance has yet to be defined. To provide insights in this ...