Of these, the best characterized are the telomere-associated proteinaceous complexes such as shelterin, CST (Cdc13 (Ctc1)/Stn1/Ten1) and the Ku70/80 heterodimer, which work in concert to ensure that telomeres avoid being recognized as DSBs ( Giraud-Panis et al., 2010). Many present-day eukaryotes have developed several lines of defense devoted to protecting telomeres from deleterious repair. With the evolution of linear genomes, cells were faced with the immediate challenge of sequestering the exposed chromosome ends away from DNA repair activities such as non-homologous end joining (NHEJ) and homology directed repair (HDR). Telomeres protect the ends of chromosomes from being recognized as DNA double-strand breaks (DSBs) and thereby prevent the faulty repair of chromosome ends ( de Lange, 2009). We speculate about how the manipulation of the telomere loop may have therapeutic implications in terms of diseases associated with telomere dysfunction and uncontrolled proliferation. In the following “perspective” we outline what is known about telomere looping and highlight the latest results regarding the regulation of this chromosome end structure. Recent work in yeast and mouse cells has uncovered additional regulatory factors that affect the loop structure at telomeres. Until recently, the only factor known to influence telomere looping in human cells was TRF2, a component of the shelterin complex. Therefore, the coordinated regulation of telomere loop formation, maintenance, and resolution is required in order to establish a balance between protecting the chromosome ends and promoting their duplication prior to cell division. Although the telomere loop has been implicated in the protection of chromosome ends from nuclease-mediated resection and unscheduled DNA repair activities, it potentially poses an obstacle to the DNA replication machinery during S-phase. The DNA at the ends of linear chromosomes (the telomere) folds back onto itself and forms an intramolecular lariat-like structure.
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Allianz, Heidelberg, Germany.
Sarah Luke-Glaser, Heiko Poschke and Brian Luke*
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