Radiation-induced DNA Damage and Its Repair

Abstract

Application of modern methods of organic chemistry and recombinant DNA technologies has provided new insights in the field of DNA radiation damage and its repair. An overview of the chemical nature of the lesions inflicted on DNA by ionizing radiation is presented. The structures of 29 different DNA modified base or sugar residues are shown in comprehensive formation schemes. A fraction of radiation-induced modified bases is spontaneously released from the DNA chain during irradiation. Another part remains attached to the DNA chain backbone and for its characterization mild formic acid or enzymatic hydrolysis have been used. Starting from the chemical formulae of the altered base residues, the specific repair enzymes and their modes of action are discussed. Various glycosylases and endonucleases have been purified to homogeneity, and in some cases the gene which encodes the protein cloned. Using methods derived from Maxam and Gilbert sequencing procedures and DNA fragment 32P-labelled at one end, it has been shown that the alkali-labile sites in DNA induced by radiation are strongly dependent on the DNA base sequence. Enzymatic methods have been used to analyse the DNA base defects produced by gamma-irradiation of cells under in vivo conditions. Structures of modified bases were the same as those observed when DNA was irradiated in aqueous solution.

Chemical Transformations Drive Complex Self-Assembly of Uracil on Close-Packed Coinage Metal Surfaces

“…The angle between the analyzer entrance lens and the incoming photon beam was 45 • in the horizontal plane. To ensure that our measurements were not compromised by molecular beam damage, as it has been reported for this kind of molecule, 47 we performed our measurements in lowalpha operation mode (beam current after injection 15 to 40 mA vs 300 mA in normal-mode operation). The absence of beam damage was further confirmed by monitoring the consistency of the data.…”

Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis

“…AP sites are considered to be both cytotoxic and mutagenic, and they have been estimated to occur spontaneously at a rate of approximately 104 cell-' day-' from the mammalian cell genome (Loeb et al, 1986). Reactive oxygen species generated either during normal cellular metabolism or by exogenous agents, such as ionizing radiation, can increase this high error rate still further (Hutchinson, 1985;Teoule, 1987).There are specific DNA repair enzymes that recognize AP sites. The major human AP endonuclease (HAPI), also known as APE, APEX or Ref-1, is a 37-kDa protein that shows strong primary sequence similarity to Escherichia coli exonuclease III protein (Demple et al, 1991;Seki et al, 1991; Correspondence to: AL Harris residue is subsequently removed by a phosphodiesterase, followed by filling in of the nucleotide gap by DNA polymerase and DNA ligase, which seals the nick and permits the accurate progress of a DNA replication fork.…”

“…AP sites are considered to be both cytotoxic and mutagenic, and they have been estimated to occur spontaneously at a rate of approximately 104 cell-' day-' from the mammalian cell genome (Loeb et al, 1986). Reactive oxygen species generated either during normal cellular metabolism or by exogenous agents, such as ionizing radiation, can increase this high error rate still further (Hutchinson, 1985;Teoule, 1987).…”

Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution

“…These activities form the basis for using radiation in chemotherapy, and the research in this area has been frequently reviewed (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Since the mid-1950s there have been studies on the effects of ionizing radiation on the chemical integrity of DNA (4,5,7,9,14).…”