Mis-expession of HipHop rescues cell lethality following telomere loss. Rebeccah L. Kurzhals¹, Laura Fanti², Sergio Piminelli², Yikang Rong³, Kent Golic⁴. 1) Department of Biology, Southeast Missouri State University, Cape Girardeau, MO; 2) University of Rome, La Sapienza, Rome, Italy; 3) National Cancer Inst., Bethesda, MD 20892; 4) University of Utah, Salt Lake City, UT 84112.

   The telomere cap is a complex of proteins and nucleic acid found at chromosome ends which prevents the DNA terminus from being seen as a double strand break in need of repair. HP1, HOAP, and HipHop, among others, are critical components of this 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, primarily through Chk2 and p53. Mutation of either of the genes encoding these proteins allows for the survival and proliferation of cells that have lost a telomere. However, even in a wildtype background, a small fraction of such cells manage to evade this apoptotic response. We have developed a technique that allows for controlled loss of a single telomere during development. We wish to understand how some cells survive such 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 mis-expressed genes required for telomere maintenance while simultaneously inducing telomere loss. We found that mis-expression of HipHop, or its paralog ms(3)K81, resulted in increased survival of cells that lost a telomere. However, mis-expression of cav, the gene encoding HOAP, or Su(var)205, encoding HP1, did not significantly increase cell survival, despite the fact that HipHop and HOAP have been shown to be required for each others stability. We suggest that HipHop has the ability to seed formation of new telomeres in somatic tissue.