Telomere Formation at Broken Chromosome Ends

Drosophila Chromosome Structure Group

Telomeres play a critical role in the stabilization of chromosome ends by distinguishing a chromosome end from a 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 the cap, recognition of the chromosome end as a DSB and telomere fusions. Mutations in mu2, however, decrease the rate of DSB repair after ionizing radiation and potentiate the recovery of chromosomes that have acquired a new telomere. The deficient chromosomes arise from loss of chromosomal material distal to the radiation-induced break, including the old telomere.

Based on genetic studies, 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 observations that mu2 mutations are recessive suppressors of PEV, and that MU2 interacts in two-hybrid experiments with HP1, which is a highly conserved component of chromatin. MU2 localizes to the nucleus after transient transfection of S2 cells and during development is found in cells that are mitotically active. During meiosis, MU2 is found at phosphorylated H2Av recombination foci. Based on these data and sequence homology, it is possible that MU2 is the Drosophila homologue of the mammalian MDC1 protein.

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