How does telomere dysfunction lead to end-to-end chromosome fusions?
Because telomere function distinguishes the ends of chromosomes from DNA breaks, it would be predicted that loss of this function should allow double-strand break repair to act upon telomeres. Although a number of factors that prevent chromosome fusion have been identified, the mechanism involved in fusing dysfunctional telomeres is poorly understood. Chromosome fusion junctions from cells with dysfunctional telomeres have been isolated from S cerevisiae (Hackett et al., 2001) and mice (Hemann et al., 2001). The structures of these fusion junctions are strikingly similar, suggesting the possibility of a common mechanism for their formation. Fusion junctions from both organisms contain 0-10 bp of microhomology, characteristic of a nonhomologous end-joining mechanism. These fusions involve the loss of all telomeric and some subtelomeric sequence, as is seen for circularized chromosomes of trt- or pot1- S pombe (Baumann and Cech, 2001; Nakamura et al., 1998). This loss of sequence suggest
