The number and not the molecular structure of DNA double-strand breaks is more important for the formation of chromosomal aberrations: A hypothesis

Abstract

DNA double-strand breaks (DSB) are known to cause chromosomal aberrations (CA). The ends of DSB have different molecular structures depending on the inducing agent. Restriction endonucleases, DNase I and benzon nuclease produce DSB with 3′-OH and 5′-phosphate ends which should be easily rejoinable (“clean” DSB). Other DSB-inducing agents, such as neocarzinostatin, bleomycin and ionizing radiation induce DSB with chemically modified ends (“dirty” DSB) which are not religatable before enzymatic pruning to make them “clean”. Both “clean” and “dirty” DSB lead to CA whose quantities and distributions are quite similar. We conclude that the number and not the molecular structures of DSB are essential for the production of CA. All DSB-inducing agents discussed in this review induce exchange events in the G1 phase of the cell cycle which look like sister chromatid exchanges (SCE) and are therefore called “false” SCE. “False” SCE seem to be mainly intrachanges and would therefore outweigh the frequencies of interchanges. Consequently, the factor F of inter- to intrachanges would then be <1, indicating that the majority of DSB would lead to CA inside the chromosome domains in which they were induced and not between different chromosomes.