1. DNA Damage 1.1. Spontaneous Alterations of DNA (by Mutator Genes) 1.2. Environmental Damage to DNA 2. DNA Repair by Reversal of Damage Without Excision 2.1. Photoreactivation 2.2. Repair of O-Alkylguanine and Alkylthymine Without DNA trand Excision 3. Base Excision Repair in Non-Mammalian Cells 3.1. DNA Glycosylase in Non-Mammalian Cells 4. Base Excision Repair in Mammalian Cells 4.1. DNA Gl...

DNA damage can be caused daily by as many as one million molecular lesions per cell by normal metabolic activities and environmental factors. The uncorrected lesions in critical genes (such as tumor suppressor genes) can inhibit a cell's ability to carry out its regular function and accordingly increase the possibility of tumor formation. Detecting DNA damage is the first step towards understan...

Pharmacologic inhibition of DNA repair may increase the efficacy of many cytotoxic cancer agents. Inhibitors of DNA repair enzymes including APE1, ATM, ATR, DNA-PK and PARP have been developed and the PARP inhibitor olaparib is the first-in-class approved in Europe and the USA for the treatment of advanced BRCA-mutated ovarian cancer. Sensitive pharmacodynamic (PD) biomarkers are needed to furt...

DNA single-strand breaks containing 3'-8-oxoguanine (3'-8-oxoG) ends can arise as a consequence of ionizing radiation and as a result of DNA polymerase infidelity by misincorporation of 8-oxodGMP. In this study we examined the mechanism of repair of 3'-8-oxoG within a single-strand break using purified base excision repair enzymes and human whole cell extracts. We find that 3'-8-oxoG inhibits l...

Distortions in the DNA sequence, such as damage or mispairs, are specifically recognized and processed by DNA repair enzymes. Many repair proteins and, in particular, glycosylases flip the target base out of the DNA helix into the enzyme's active site. Our molecular dynamics simulations of DNA with intact and damaged (oxidized) methyl-cytosine show that the probability of being flipped is simil...