Regulation of the cell cycle following DNA damage in normal and Ataxia telangiectasia cells
- 1 April 1996
- journal article
- review article
- Published by Springer Nature in Cellular and Molecular Life Sciences
- Vol. 52 (4) , 316-328
- https://doi.org/10.1007/bf01919534
Abstract
A proportion of the population is exposed to acute doses of ionizing radiation through medical treatment or occupational accidents, with little knowledge of the immedate effects. At the cellular level, ionizing radiation leads to the activation of a genetic program which enables the cell to increase its chances of survival and to minimize detrimental manifestations of radiation damage. Cytotoxic stress due to ionizing radiation causes genetic instability, alterations in the cell cycle, apoptosis, or necrosis. Alterations in the G1, S and G2 phases of the cell cycle coincide with improved survival and genome stability. The main cellular factors which are activated by DNA damage and interfere with the cell cycle controls are: p53, delaying the transition through the G1-S boundary; p21WAF1/CIPI, preventing the entrance into S-phase; proliferating cell nuclear antigen (PCNA) and replication protein A (RPA), blocking DNA replication; and the p53 variant protein p53as together with the retinoblastoma protein (Rb), with less defined functions during the G2 phase of the cell cycle. By comparing a variety of radioresistant cell lines derived from radiosensitive ataxia talangiectasia cells with the parental cells, some essential mechanisms that allow cells to gain radioresistance have been identified. The results so far emphasise the importance of an adequate delay in the transition from G2 to M and the inhibition of DNA replication in the regulation of the cell cycle after exposure to ionizing radiation.Keywords
This publication has 173 references indexed in Scilit:
- Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cellsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1994
- p53 is required for radiation-induced apoptosis in mouse thymocytesNature, 1993
- Clonal chromosome aberrations and genomic instability in X-irradiated human T-lymphocyte culturesMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1993
- Evidence of different complementation groups amongst human genetic disorders characterized by radiosensitivityMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1993
- Protein kinase C mediates x-ray inducibility of nuclear signal transducers EGR1 and JUN.Proceedings of the National Academy of Sciences, 1991
- Universal control mechanism regulating onset of M-phaseNature, 1990
- Flow cytometric analysis of X-ray sensitivity in ataxia telangiectasiaMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1989
- Death and the cellImmunology Today, 1986
- Effects of X-irradiation on cell-cycle progression, induction of chromosomal aberrations and cell killing in ataxia telangiectasia (AT) fibroblastsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1985
- Comparison of kinetics of X-ray-induced cell killing in normal, ataxia telangiectasia and hereditary retinoblastoma fibroblastsMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 1983