Telomere Formation at Broken Chromosome Ends
Drosophila Chromosome Structure Group
Telomeres play a critical role in the stabilization of chromosome ends by distinguishing a natural chromosome end from a DNA double strand break (DSB). This function is known as capping. Several proteins are known to be involved the formation of the chromosome cap. A mutation in any one of these leads to loss of caps from several chromosome ends, recognition of the chromosome ends as DSBs, and fusions of the chromosome endss. Mutations in the mu2 gene, however, have essentially the opposite effect. Instead of losing telomeres from chromosome ends, these mutations potentiate the formation of new telomeres where they did not exist previously. mu2 mutations decrease the rate of DSB repair in oocytes after ionizing radiation and reduce or eliminate the level of cell cycle delay that is normally induced by the presence of a DSB. After fertilization the unrepaired broken chromosomes end acquire a new telomere. The deficient chromosomes that are formed thus arise from the loss of chromosomal material distal to the radiation-induced break, including the old telomere. The process by which the broken chromosome end acquires a new telomere is completely unknown. This process, however, does not require the presence of 'telomeric' DNA at the site of the new telomere.
Based on genetic studies (Mason et al. 1997), the group proposed that MU2 plays an important role in the repair of DSBs by controlling some aspect of the oocyte nucleus, possibly chromatin structure. This conclusion is supported by the observation that MU2 interacts in two-hybrid experiments with HP1, which is a highly conserved component of chromatin. In cultured S2 cells MU2 localizes to the nucleus in a diffuse manner but relocates to repair foci after irradiation. Based on protein binding data and sequence homology, it is possible that MU2 is the Drosophila homologue of the mammalian MDC1 protein (Dronamraju and Mason 2009).