Telomere Repeat Binding Factors

Telomere repeats are bound by the so-called shelterin multiprotein complex (de Lange et al. 2005; see also Chang, this volume). Shelterin contains factors that bind directly to both single-strand repeats, such as the Pot1/PTOP heterodimer, or to double-strand telomeric repeats such as the telomere binding factors TRF1 and TRF2 and their interacting proteins Rap1 (repressor/activator protein 1) and Tin2 (TRF1-Interacting Nuclear Factor 2) (Fig. 12.1) (de Lange et al. 2005). TRF1 also interacts with the TANK1 and TANK2 poly(ADP)-ribosylases (also known as tankyrases) (Smith et al. 1998). TRF1 and the TRF1-interacting proteins have been proposed to regulate telomere length, probably by controlling the access of telom-erase to the telomere (Smogorzewska et al. 2000).

TRF2 and Pot1 have additional roles in telomere protection, as indicated by the fact that they prevent end-to-end chromosome fusions (van Steensel et al. 1998, Celli et al. 2005, Hockemeyer et al. 2006). The mechanisms underlying the roles of TRF2 and Pot1 in telomere protection may be related to their interplay with DNA-damage signaling and repair factors (reviewed in Blasco 2005). In particular, TRF2 can interact with components of the Mre11 complex (meiotic recombination 11) (Zhu et al. 2000), which is central to both nonhomologous end joining (NHEJ) and homologous recombination (HR). TRF2 has been proposed to bind to ATM and to cancel the ATM-triggered damage response, suggesting that TRF2 has a role in preventing a DNA damage response at telomeres (Karlseder et al. 2004, Bradshaw et al. 2005). Pot 1 has recently been proposed to provide a similar function, as indicated by the fact that Pot1-deficient mice show increased DNA damage signaling at telomeres (Hockemeyer et al. 2006; see also Chang, this volume).

In addition to the shelterin proteins, components of the NHEJ (Ku and DNA-PKcs) and HR (Rad51D, Rad54) pathways have been also shown to have roles in telomere length regulation and telomere capping (Bailey et al. 2001, Samper et al. 2000, Tarsounas et al. 2004, Jaco et al. 2003).

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