The telomere is a complex structure at the end of linear chromosomes which is specialized for several roles. Telomeres facilitate the complete replication of the ends of the linear chromosomal DNA and thus prevent progressive loss of terminal nucleotides in each round of replication. They also act as """"""""chromosome caps"""""""", because the terminal DNA of chromosome ends cannot be linked to other DNA. Such caps appear to be necessary for chromosome stability since non-telomeric ends of broken chromosomes fuse with other broken ends. Telomeres also engage in telomere-to-telomere and telomere-to-nuclear membrane associations which may play a role in nuclear organization. We propose to study the structure of the Drosophila telomere and the healing mechanism of chromosome breaks. We believe that both are intimately related and that by analyzing the behavior of chromosomes that have lost their telomere we will learn a great deal about de novo telomere formation and their maintenance. Based on our previous observations we are presenting a new model of Drosophila telomere elongation by proposing that the two aspects which we have observed at broken chromosome ends, namely progressive loss of nucleotides and transpositions of HeT-A retroposons, may also apply to natural chromosome ends. Thus, continuous loss of terminal nucleotides due to incomplete DNA replication of the ends can be balanced by frequent transposition of HeT-A retroposons to these ends. We will further characterize the recently discovered HeT-A retroposons whose members are associated with natural telomeres and can transpose to broken chromosome ends. Cross-reaction with an oligonucleotide from a highly conserved region of the Drosophila HeT-A element will be performed to screen for related retroposons in other insects and invertebrates. We will also study the molecular basis of the """"""""capping"""""""" mechanism of chromosomes. We propose to initiate a molecular analysis of the mutator-2 locus which enabled us to recover terminal chromosome deficiencies. We will thus obtain insights into the mechanisms of chromosome break repair, de novo telomere formation, and chromosome """"""""capping"""""""".
| Biessmann, H; Mason, J M (1994) Telomeric repeat sequences. Chromosoma 103:154-61 |
| Wang, M; Champion, L E; Biessmann, H et al. (1994) Mapping a mutator, mu2, which increases the frequency of terminal deletions in Drosophila melanogaster. Mol Gen Genet 245:598-607 |
| Biessmann, H; Kasravi, B; Bui, T et al. (1994) Comparison of two active HeT-A retroposons of Drosophila melanogaster. Chromosoma 103:90-8 |
| Biessmann, H; Kasravi, B; Jakes, K et al. (1993) The genomic organization of HeT-A retroposons in Drosophila melanogaster. Chromosoma 102:297-305 |
