Molecular targets in cellular response to ionizing radiation and implications in space radiation protection.
DNA repair systems and cell cycle checkpoints closely co-operate in the attempt of maintaining the genomic integrity of cells damaged by ionizing radiation. DNA double-strand breaks (DSB) are considered as the most biologically important radiation-induced damage. Their spatial distribution and association with other types of damage depend on radiation quality. It is believed these features affect damage reparability, thus explaining the higher efficiency for cellular effects of densely ionizing radiation with respect to gamma-rays. DSB repair systems identified in mammalian cells are homologous recombination (HR), single-strand annealing (SSA) and non-homologous end-joining (NHEJ). Some enzymes may participate in more than one of these repair systems. DNA damage also triggers biochemical signals activating checkpoints responsible for delay in cell cycle progression that allows more time for repair. Those at G1/S and S phases prevent replication of damaged DNA and those at G2/M phase prevent segregation of changed chromosomes. Individuals with lack or alterations of genes involved in DNA DSB repair and cell cycle checkpoints exhibit syndromes characterized by genome instability and predisposition to cancer. Information reviewed in this paper on the basic mechanisms of cellular response to ionizing radiation indicates their importance for a number of issues relevant to protection of astronauts from space radiation.
Belli
Mauro
M
Physics Laboratory, Istituto Superiore di Sanità, 00161 Rome, Italy. mauro.belli@iss.it
Sapora
Orazio
O
Tabocchini
Maria Antonella
MA
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D002468:Cell Physiological Phenomena / Q000528:radiation effects; D002477:Cells / Q000528:radiation effects*; D003359:Cosmic Radiation / Q000009:adverse effects; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D011835:Radiation Protection; D013026:Space Flight
D004247:DNA