The telomere cap is a complex of proteins and nucleic acids found at chromosome ends which prevents the DNA terminus from being seen as a double strand break in need of repair. HP1, HOAP, HipHop, Ver, and Moi are components of the capping complex. In most cells the absence of a single telomere cap is sufficient to trigger apoptosis. Cells that do not die are likely to experience end-to-end fusions of uncapped ends, leading to gross chromosomal rearrangements and genomic instability. The apoptotic response to telomere loss or dysfunction is mediated by the DNA damage response pathway. However, even in a wildtype background, a small fraction of such cells manage to evade this apoptotic response.
We developed a technique that allows for controlled loss of a single telomere during development. We wish to understand how some cells survive telomere loss. Immunostaining for the telomere cap component HOAP revealed that in some somatic cells, non-telomeric ends can be healed by the addition of a new cap. To characterize this process, we misexpressed genes required for telomere maintenance, while simultaneously inducing telomere loss. We found that misexpression of HipHop, or its paralog ms(3)K81, resulted in increased survival of cells that lost a telomere. However, misexpression of cav, the gene encoding HOAP or Su(var)205, the gene encoding HP1, or ver, did not significantly increase cell survival. We suggest that HipHop has the ability to seed formation of new telomeres in somatic tissue.
In order to determine if proteins required for telomere maintenance are limiting for HipHop to suppress of cell death after telomere loss, we misexpressed hiphop while simultaneously inducing telomere loss in flies that are heterozygous for mutations in tefu, mre11, nbs, and cav. Initial results suggest that these genes do not significantly affect cell survival following telomere loss. We are currently testing other genes required for telomere maintenance. In the absence of misexpression of hiphop, cell survival is not significantly different in flies that are heterozygous for mutations in tefu, mre11, nbs, cav, hiphop, or Su(var)205 following telomere loss. The telomere cap components tested to date do not appear to be limiting for HipHop’s role in suppressing cell lethality after telomere loss.