DRUSE

Simon Titen and Kent Golic studied telomere loss by breakage of an induced dicentric chromosome in the fruitfly Drosophila melanogaster [Genetics 2008 Dec;180(4):1821-32; Epub 2008 Oct 9]. They found that one outcome of this is cell death through Chk2 and Chk1 controlled p53-dependent apoptotic pathways. Yet they also observed escape from apoptosis and repeated division in some cells that have lost a telomere. This evasion of apoptosis is accompanied by abnormalites such as chromosome fusions, anaphase bridges, aneuploidy, and polyploidy. They also found evidence of bridge–breakage–fusion cycles and chromosome segments without centromeres. They further noted that cells manifesting these signs of genomic instability were much more frequent when the apoptotic mechanisms were crippled. In the end, they concluded that the loss of a single telomere is sufficient to generate genomic instability involving multiple chromosomes and aneuploidy.

They used the FLP recombinase system to examine the cellular responses to loss of a single telomere. This generates a chromosome end lacking a telomere. Synthesis of FLP recombinase is induced by heat shock, which causes recombination between inverted FRTs on sister chromatids to generate dicentric and acentric chromosomes. They believe their strategy closely mimics the situation faced by a mammalian cell in which a single telomere becomes critically short and dysfunctional due to incomplete replication in the absence of telomerase.

Figure 1. Dicentric/acentric chromosome production and segregation. FLP-induced recombination between oppositely oriented FRTs on sister chromatids produces a dicentric chromosome and an acentric chromosome. At anaphase the dicentric chromosome is stretched between the poles and usually breaks. Centromeres are indicated as filled circles, telomeres as filled squares, FRTs as arrows.