Fission Yeast Pot1-Tpp1 Protects Telomeres and Regulates Telomere Length

Abstract

Telomeres are specialized chromatin structures that protect chromosomal ends. Protection of telomeres 1 (Pot1) binds to the telomeric G-rich overhang, thereby protecting telomeres and regulating telomerase. Mammalian POT1 and TPP1 interact and constitute part of the six-protein shelterin complex. Here we report that Tpz1, the TPP1 homolog in fission yeast, forms a complex with Pot1. Tpz1 binds to Ccq1 and the previously undiscovered protein Poz1 (Pot1-associated in Schizosaccharomyces pombe), which protect telomeres redundantly and regulate telomerase in positive and negative manners, respectively. Thus, the Pot1-Tpz1 complex accomplishes its functions by recruiting effector molecules Ccq1 and Poz1. Moreover, Poz1 bridges Pot1-Tpz1 and Taz1-Rap1, thereby connecting the single-stranded and double-stranded telomeric DNA regions. Such molecular architectures are similar to those of mammalian shelterin, indicating that the overall DNA-protein architecture is conserved across evolution.

PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase

“…Our findings further strengthens the detailed mechanism of Tel1/Cdc13/Est1-mediated telomerase recruitment in S. cerevisiae 20,22,23,25 . The collective functions of Ccq1, Tpp1and Pot1 in Schizosaccharomyces pombe are analogous to the telomeric role of Cdc13 in S. cerevisiae 49,50 . Consistently, ataxia telangiectasia mutated (ATM)/ATM-and Rad3-related (ATR)-promoted Ccq1-Est1 interaction was recently revealed 51 .…”

Replication of Telomeres and the Regulation of Telomerase

“…Telomerase recruitment to telomeres in S. pombe occurs through the interaction of the telomerase subunit Est1 with Ccq1, which is tethered to telomeres through the interaction with Tpz1, which in turn interacts with Pot1 and Poz1 (Miyoshi et al 2008;Tomita and Cooper 2008;Webb and Zakian 2012). Importantly, S. pombe Tel1 (ortholog of mammalian Atm) and Rad3 (ortholog of mammalian Atr) promote the direct interaction between Ccq1 and the Est1 subunit of telomerase (Moser et al 2011;Yamazaki et al 2012).…”

“…1). Rap1 binds Poz1, Poz1 binds Tpz1, and Tpz1 interacts with Ccq1 and Pot1 (Miyoshi et al 2008). Pot1 also binds the telomeric single-stranded 3 0 overhang (Baumann and Cech 2001).…”

A genome-wide screen for Schizosaccharomyces pombe deletion mutants that affect telomere length

“…Fission yeast telomerase is composed of the catalytic subunit Trt1, the RNA template TER1, and an accessory protein subunit Est1 [7]. In addition to telomerase, other proteins and their complexes involved in telomere-length regulation include Poz1, Pot1-Tpz1-Ccq1 complex, Taz1-Rap1 complex [9] and Stn1-Ten1 complex [10]. To systematically search for genes that affect telomeres, we have performed Southern blot analysis to examine telomere-length changes in a collection of 2 814 haploid deletion strains of S. pombe (see Supplementary information, Data S1).…”