Rejoining of DNA double‐strand breaks in human fibroblasts and its impairment in one ataxia telangiectasia and two fanconi strains

Abstract

Using the technique of neutral elution through polycarbonate filters as a measure of DNA length, and hence of the number of double-strand breaks incurred as a result of radiation damage, we found that normal human fibroblasts rejoin 50% of all breaks within only 3 min (37 degrees C). This fast rejoining was impaired in fibroblasts from one patient with Ataxia telangiectasia and in fibroblasts from two patients with Fanconi's anemia. Also the number of residual breaks after several hours of repair was higher than in control cells. Other cases with the same diseases were normal in their rejoining of double-strand breaks.

Radiation Response in Vitro of Fibroblasts from a Fanconi Anemia Patient with Marked Clinical Radiosensitivity

“…In addition, alterations of the FA protein complex can also affect chromatin transformation during replication and DNA damage repair. The slow kinetics of the restitution of DNA damage in irradiated FA cells shown here by the Comet assay ( Figure 2) is in line with the defects of the DNA repair mechanism earlier reported for FA cells [13,42]. As shown recently, the repair of DNA DSBs by homologous recombination in FA cells is altered [14,18,52].…”

Chromatid damage after G2 phase x-irradiation of cells from cancer-prone individuals implicates deficiency in DNA repair.

“…Additionally, cells from another cancer-prone genetic disorder, ataxia telangiectasia, as well as FA cells were shown previously to develop chromatid breaks or gaps after xirradiation during G2 (3,8,9). The higher incidence of chromatid breaks in these previous studies probably resulted from the longer irradiation-fixation interval, [3][4][5][6] study. During this longer interval, gaps could be converted into breaks (11).…”

“…A deficiency in the repair of UV-induced DNA damage was described in 1968 (1) in cells from XP individuals with a high incidence of skin cancer. Subsequently, studies on ataxia telangiectasia and FA cells provided some evidence that these cells may be defective in repair of DNA damage produced by ionizing radiation or DNA crosslinking agents (2)(3)(4)(5)(6)(7)(8)(9). However, numerous attempts with biochemical methods have failed to reveal a DNA repair deficiency(ies) in all of these genetic disorders.…”

Cell cycle dependent DNA break increase in ataxia telangiectasia lymphoblasts after radiation exposure

“…Thus, the existence of a highly damaged subpopulation helps to explain seemingly contradictory notions of normal repair, 4-9 but increased DNA break numbers soon after irradiation. [10][11][12][13] However, another reason for discordant observations with respect to DNA repair in AT might be the use of cycling versus non-cycling AT cells in diVerent reports. Our study was carried out to determine whether the cell cycle influences the numbers of DNA breaks detected in irradiated AT cells.…”