Advances in the biophysical and molecular bases of radiation cytogenetics

Abstract

Purpose: For more than 70 years radiation cytogenetics has continued to be a topic of major concern in relation to the action of radiation on living cells. To date, diverse cytogenetic findings have developed into orderly, quantitative interpretations and have stimulated numerous biophysical models. However, it is generally agreed that any one of the models used alone is still unable to explain all aspects of the observed chromosomal effects. In this review, a large number of radiation-induced chromosome aberration findings from the literature are reassessed with special attention given to the reaction kinetics and the relevant molecular processes.

Conclusion: It is now clear that DNA double-strand breaks (DSB) are an integral component of radiation-induced chromosome aberration. At the nexus of the maintenance of genome integrity, cells are equipped with excellent systems to repair DSB, notably non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). These repair mechanisms are strictly regulated along with the DNA turnover cycle. NHEJ functions in all phases of the cell cycle, whereas HRR has a supplementary role specifically in S/G2 phase, where homologous DNA sequences are available in close proximity. The repair pathways are further regulated by a complex nuclear dynamism, where DSB are sensed and large numbers of repair proteins are recruited and assembled to form a repair complex involving multiple DSB. Considering such DSB repair dynamism, radiation-induced chromosome aberrations could be well understood as DSB-DSB pairwise interactions associated with the NHEJ pathway in all phases of the cell cycle and misrepair of a single DSB associated with the complementary HRR pathway in late S/G2 phase.

Keywords:

• Radiation
• chromosome aberrations
• breakage-reunion
• DNA double-strand breaks
• non-homologous end-joining
• homologous recombination