On the nature of visible chromosomal gaps and breaks.

From the earliest days of chromosomal aberration studies, the distinction, nature and origin of light-microscope observed "gaps" and "breaks" have been topics for debate and controversy. In this paper we survey, briefly, the various ideas that have appeared in the very extensive literature, and attempt to evaluate them in the light of our current understanding of chromosome structure and aberration formation. Attention is drawn to the problems of interpretation caused by G2/S cell imprecision.

Chromosomal aberrations: formation, identification and distribution.

Chromosomal aberrations (CA) are the microscopically visible part of a wide spectrum of DNA changes generated by different repair mechanisms of DNA double strand breaks (DSB). The method of fluorescence in situ hybridisation (FISH) has uncovered unexpected complexities of CA and this will lead to changes in our thinking about the origin of CA. The inter- and intrachromosomal distribution of breakpoints is generally not random. CA breakpoints occur preferentially in active chromatin. Deviations from expected interchromosomal distributions of breakpoints may result from the arrangement of chromosomes in the interphase nucleus and/or from different sensitivities of chromosomes with respect to the formation of CA. Telomeres and interstitial telomere repeat like sequences play an important role in the formation of CA. Subtelomeric regions are hot spots for the formation of symmetrical exchanges between homologous chromatids and cryptic aberrations in these regions are associated with human congenital abnormalities.