Tel1ATM and Rad3ATR kinases promote Ccq1-Est1 interaction to maintain telomeres in fission yeast

Moser, Bettina A.; Chang, Ya-Ting; Kosti, Jorgena; Nakamura, Toru

doi:10.1038/nsmb.2187

Cited by 79 publications

(202 citation statements)

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“…4D). We reasoned that the different behavior of ccq1D and ccq1-T93A is because Ccq1 is also part of the SHREC complex involved in telomere silencing (Sugiyama et al 2007; Motamedi et al 2008), which is not affected by the ccq1-T93A mutation (Moser et al 2011;Yamazaki et al 2012). Consistent with this idea, we also found that sde2D, which resulted in selective loss of telomere silencing (SugiokaSugiyama and Sugiyama 2011), was able to bypass RNAi for pericentric heterochromatin formation (Supplemental Table S1; Fig.…”

Section: Elimination Of Other Shelterin Components Also Bypasses Rnaisupporting

confidence: 75%

“…Rap1 and Poz1 form a bridge that connects Taz1 and Pot1-Tpz1 complexes (Miyoshi et al 2008). Pot1-Tpz1 associates with Ccq1 to recruit telomerase Trt1, which uses associated RNA as a template to elongate the telomere overhang (Nakamura et al 1997;Miyoshi et al 2008;Tomita and Cooper 2008;Moser et al 2011;Yamazaki et al 2012). By ChIP analyses, we found that Poz1 was enriched at telomeres, as expected, but not detected at pericentric repeats, even in dcr1D cells (Fig.…”

Section: Elimination Of Other Shelterin Components Also Bypasses Rnaisupporting

confidence: 49%

“…S4), indicating the requirement of RNAi-independent pericentric heterochromatin pathways. In contrast, trt1D and a ccq1-T93A mutant, which attenuated recruitment of Trt1 to telomeres (Moser et al 2011;Yamazaki et al 2012), had no effect on this process (Fig. 4D).…”

Section: Elimination Of Other Shelterin Components Also Bypasses Rnaimentioning

confidence: 91%

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Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

et al. 2013

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The RNAi pathway is required for heterochromatin assembly at repetitive DNA elements in diverse organisms. In fission yeast, loss of RNAi causes pericentric heterochromatin defects, compromising gene silencing and chromosome segregation. Here we show that deletion of telomere shelterin components restores pericentric heterochromatin and its functions in RNAi mutants. We further isolated a separation-of-function mutant of Poz1 and revealed that defective telomere silencing, but not telomere length control, is critical for bypassing RNAi. Further analyses demonstrated that compromising shelterin-mediated heterochromatin assembly in RNAi mutants releases heterochromatin protein Swi6, which is redistributed to pericentric regions through RNAiindependent heterochromatin assembly pathways. Given the high mobility of Swi6 protein and that increased levels of Swi6 facilitates heterochromatin spreading as well as ectopic heterochromatin assembly, our results suggest that constitutive heterochromatin domains use multiple pathways to form high-affinity platforms to restrain Swi6, thus limiting its availability and avoiding promiscuous heterochromatin formation.

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Section: Elimination Of Other Shelterin Components Also Bypasses Rnaisupporting

confidence: 75%

Section: Elimination Of Other Shelterin Components Also Bypasses Rnaisupporting

confidence: 49%

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Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

et al. 2013

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“…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). Ccq1 is phosphorylated on T93 by Tel1 and Rad3, and mutation of this site abolishes telomerase recruitment.…”

Section: S Pombementioning

confidence: 99%

Replication of Telomeres and the Regulation of Telomerase

Pfeiffer

Lingner

2013

Cold Spring Harbor Perspectives in Biology

112

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Telomeres are the physical ends of eukaryotic chromosomes. They protect chromosome ends from DNA degradation, recombination, and DNA end fusions, and they are important for nuclear architecture. Telomeres provide a mechanism for their replication by semiconservative DNA replication and length maintenance by telomerase. Through telomerase repression and induced telomere shortening, telomeres provide the means to regulate cellular life span. In this review, we introduce the current knowledge on telomere composition and structure. We then discuss in depth the current understanding of how telomere components mediate their function during semiconservative DNA replication and how telomerase is regulated at the end of the chromosome. We focus our discussion on the telomeres from mammals and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe.

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“…Whereas Taz1 binds to double-stranded G-rich telomeric repeats, Pot1 binds to 3′ single-stranded overhang telomeric DNA, known as G-tails (8,9). Rap1, Poz1, and Tpz1 act as a molecular bridge connecting Taz1 and Pot1 through protein-protein interactions (7), and Ccq1 contributes to telomerase recruitment via Rad3 ATR /Tel1 ATM -dependent interaction with the telomerase regulatory subunit Est1 (10).…”

mentioning

confidence: 99%

SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1 ^Tpp1 to modulate shelterin–Stn1 interaction in fission yeast

Miyagawa

Low

Santosa

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Telomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure complete replication of the terminal DNA through recruitment of telomerase. The regulation of telomerase is a critical area of telomere research and includes cis regulation by the shelterin complex in mammals and fission yeast. We have identified a key component of this regulatory pathway as the SUMOylation [the covalent attachment of a small ubiquitin-like modifier (SUMO) to target proteins] of a shelterin subunit in fission yeast. SUMOylation is known to be involved in the negative regulation of telomere extension by telomerase; however, how SUMOylation limits the action of telomerase was unknown until now. We show that SUMOylation of the shelterin subunit TPP1 homolog in Schizosaccharomyces pombe (Tpz1) on lysine 242 is important for telomere length homeostasis. Furthermore, we establish that Tpz1 SUMOylation prevents telomerase accumulation at telomeres by promoting recruitment of Stn1-Ten1 to telomeres. Our findings provide major mechanistic insights into how the SUMOylation pathway collaborates with shelterin and Stn1-Ten1 complexes to regulate telomere length.CST complex | DNA replication | S-phase | cell cycle T elomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure replication of the terminal DNA (1, 2). In most eukaryotes, telomere length is maintained predominantly by telomerase, a specialized reverse transcriptase that adds telomeric DNA to the 3′ ends of chromosomes. In addition, a DNA homologous recombination (HR)-dependent mechanism, known as the alternative lengthening of telomeres (ALT) pathway, may contribute to telomere maintenance (3). Given the significant contribution of dysfunctional telomeres to genome instability, cancer development, and aging (4), understanding how telomere maintenance and the cellular response to telomere dysfunction is important. Maintenance of stable telomere length requires a balance of positive and negative regulators of telomerase. The molecular details of such regulation are not completely understood, however, and further investigation of how telomeres ensure genomic integrity is needed.Telomere regulation is largely mediated by the shelterin complex specifically bound to telomeric repeats (2). In mammalian cells, the shelterin complex (composed of TRF1, TRF2, RAP1, TIN2, TPP1, and POT1) plays critical roles in (i) regulating telomerase recruitment, (ii) preventing full-scale activation of DNA damage checkpoint responses by checkpoint kinases ATM and ATR, (iii) preventing DNA resection, and (iv) preventing telomere rearrangement and fusion by HR, classical nonhomologous end-joining (NHEJ), or alternative NHEJ (2, 5, 6).Fission yeast Schizosaccharomyces pombe serves as an attractive model system for studying telomere regulation, because it uses a complex that closely resembles the mammalian shelterin (7). Fission yeast shelterin is composed of Taz1 (an ortholog of TRF1 and TRF2), Rap1, Poz1 (a possible analog of TIN2), TPP...

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Tel1ATM and Rad3ATR kinases promote Ccq1-Est1 interaction to maintain telomeres in fission yeast

Cited by 79 publications

References 41 publications

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Replication of Telomeres and the Regulation of Telomerase

SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1 ^Tpp1 to modulate shelterin–Stn1 interaction in fission yeast

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Tel1ATM and Rad3ATR kinases promote Ccq1-Est1 interaction to maintain telomeres in fission yeast

Cited by 79 publications

References 41 publications

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly

Replication of Telomeres and the Regulation of Telomerase

SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1 Tpp1 to modulate shelterin–Stn1 interaction in fission yeast

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SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1 ^Tpp1 to modulate shelterin–Stn1 interaction in fission yeast