Fission Yeast Taz1 and RPA Are Synergistically Required to Prevent Rapid Telomere Loss

The telomere complex must allow nucleases and helicases to process chromosome ends to make them substrates for telomerase, while preventing these same activities from disrupting chromosome end-protection. Replication protein A (RPA) binds to single-stranded DNA and is required for DNA replication, recombination, repair, and telomere maintenance. In fission yeast, the telomere binding protein Taz1 protects telomeres and negatively regulates telomerase. Here, we show that taz1-d rad11-D223Y double mutants lose their telomeric DNA, indicating that RPA (Rad11) and Taz1 are synergistically required to prevent telomere loss. Telomere loss in the taz1-d rad11-D223Y double mutants was suppressed by additional mutation of the helicase domain in a RecQ helicase (Rqh1), or by overexpression of Pot1, a single-strand telomere binding protein that is essential for protection of chromosome ends. From our results, we propose that in the absence of Taz1 and functional RPA, Pot1 cannot function properly and the helicase activity of Rqh1 promotes telomere loss. Our results suggest that controlling the activity of Rqh1 at telomeres is critical for the prevention of genomic instability.

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Fission yeast telomere-binding protein Taz1 is a functional but not a structural counterpart of human TRF1 and TRF2

Cell Research ◽

10.1038/cr.2015.76 ◽

2015 ◽

Vol 25 (7) ◽

pp. 881-884 ◽

Cited By ~ 8

Author(s):

Wei Deng ◽

Jian Wu ◽

Feng Wang ◽

Junko Kanoh ◽

Pierre-Marie Dehe ◽

...

Keyword(s):

Fission Yeast ◽

Binding Protein ◽

Telomere Binding Protein ◽

Yeast Telomere

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Evolutionary-conserved telomere-linked helicase genes of fission yeast are repressed by silencing factors, RNAi components and the telomere-binding protein Taz1

Nucleic Acids Research ◽

10.1093/nar/gkj415 ◽

2006 ◽

Vol 34 (1) ◽

pp. 78-88 ◽

Cited By ~ 53

Author(s):

K. R. Hansen

Keyword(s):

Fission Yeast ◽

Binding Protein ◽

Telomere Binding Protein

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Recombination-Based Telomere Maintenance Is Dependent on Tel1-MRN and Rap1 and Inhibited by Telomerase, Taz1, and Ku in Fission Yeast

Molecular and Cellular Biology ◽

10.1128/mcb.01614-07 ◽

2007 ◽

Vol 28 (5) ◽

pp. 1443-1455 ◽

Cited By ~ 25

Author(s):

Lakxmi Subramanian ◽

Bettina A. Moser ◽

Toru M. Nakamura

Keyword(s):

Dna Repair ◽

Fission Yeast ◽

Catalytic Subunit ◽

Telomere Maintenance ◽

Yeast Cells ◽

Eukaryotic Cells ◽

Checkpoint Kinase ◽

Telomere Binding Protein ◽

Evolutionarily Conserved ◽

Linear Chromosomes

ABSTRACT Fission yeast cells survive loss of the telomerase catalytic subunit Trt1 (TERT) through recombination-based telomere maintenance or through chromosome circularization. Although trt1Δ survivors with linear chromosomes can be obtained, they often spontaneously circularize their chromosomes. Therefore, it was difficult to establish genetic requirements for telomerase-independent telomere maintenance. In contrast, when the telomere-binding protein Taz1 is also deleted, taz1Δ trt1Δ cells are able to stably maintain telomeres. Thus, taz1Δ trt1Δ cells can serve as a valuable tool in understanding the regulation of telomerase-independent telomere maintenance. In this study, we show that the checkpoint kinase Tel1 (ATM) and the DNA repair complex Rad32-Rad50-Nbs1 (MRN) are required for telomere maintenance in taz1Δ trt1Δ cells. Surprisingly, Rap1 is also essential for telomere maintenance in taz1Δ trt1Δ cells, even though recruitment of Rap1 to telomeres depends on Taz1. Expression of catalytically inactive Trt1 can efficiently inhibit recombination-based telomere maintenance, but the inhibition requires both Est1 and Ku70. While Est1 is essential for recruitment of Trt1 to telomeres, Ku70 is dispensable. Thus, we conclude that Taz1, TERT-Est1, and Ku70-Ku80 prevent telomere recombination, whereas MRN-Tel1 and Rap1 promote recombination-based telomere maintenance. Evolutionarily conserved proteins in higher eukaryotic cells might similarly contribute to telomere recombination.

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1P215 Tetraplex of fission yeast telomeric DNA and unfolding of the tetraplex on the interaction with telomeric DNA binding protein Pot1(7. Nucleic acid binding protein,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)

Seibutsu Butsuri ◽

10.2142/biophys.46.s200_3 ◽

2006 ◽

Vol 46 (supplement2) ◽

pp. S200

Author(s):

Ayako Furukawa ◽

Hidetaka Torigoe

Keyword(s):

Nucleic Acid ◽

Dna Binding ◽

Fission Yeast ◽

Poster Session ◽

Binding Protein ◽

Dna Binding Protein ◽

Nucleic Acid Binding ◽

Telomeric Dna ◽

Acid Binding Protein ◽

Meeting Program

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SLX4IP promotes RAP1 SUMOylation by PIAS1 to coordinate telomere maintenance through NF-κB and Notch signaling

Science Signaling ◽

10.1126/scisignal.abe9613 ◽

2021 ◽

Vol 14 (689) ◽

pp. eabe9613

Author(s):

Nathaniel J. Robinson ◽

Masaru Miyagi ◽

Jessica A. Scarborough ◽

Jacob G. Scott ◽

Derek J. Taylor ◽

...

Keyword(s):

Notch Signaling ◽

Intracellular Signaling ◽

Binding Protein ◽

Telomere Maintenance ◽

Nucleocytoplasmic Shuttling ◽

Iκb Kinase ◽

Alternative Lengthening ◽

Telomere Binding Protein ◽

Sumo Ligase

The maintenance of telomere length supports repetitive cell division and therefore plays a central role in cancer development and progression. Telomeres are extended by either the enzyme telomerase or the alternative lengthening of telomeres (ALT) pathway. Here, we found that the telomere-associated protein SLX4IP dictates telomere proteome composition by recruiting and activating the E3 SUMO ligase PIAS1 to the SLX4 complex. PIAS1 SUMOylated the telomere-binding protein RAP1, which disrupted its interaction with the telomere-binding protein TRF2 and facilitated its nucleocytoplasmic shuttling. In the cytosol, RAP1 bound to IκB kinase (IKK), resulting in activation of the transcription factor NF-κB and its induction of Jagged-1 expression, which promoted Notch signaling and the institution of ALT. This axis could be targeted therapeutically in ALT-driven cancers and in tumor cells that develop resistance to antitelomerase therapies. Our results illuminate the mechanisms underlying SLX4IP-dependent telomere plasticity and demonstrate the role of telomere proteins in directly coordinating intracellular signaling and telomere maintenance dynamics.

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