DNA DOUBLE-STRAND BREAKS, CHROMOSOMAL REARRANGEMENTS, AND GENOMIC INSTABILITY

DNA double-strand breaks can lead to chromosomal rearrangements at the first mitosis after exposure to the DNA strand-breaking agent. The ev idence suggests a number of different pathways for DNA double-strand b reak rejoining in mammalian cells, but it is unclear what factors dete rmine the fate of the induced break and whether or not it will lead to chromosomal rearrangement. If a cell does survive and proliferate aft er DNA cleavage, delayed chromosomal instability can be observed in th e clonal descendants of the exposed cell. Most, but not all DNA double -strand breaking agents are effective at inducing this delayed chromos omal instability. In this paper, we review the evidence for the role o f the DNA double-strand break in directly induced and delayed chromoso mal rearrangements. (C) 1998 Elsevier Science B.V. All rights reserved .