scholarly journals CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length

Aging Cell ◽  
2018 ◽  
Vol 17 (4) ◽  
pp. e12783 ◽  
Author(s):  
Peili Gu ◽  
Shuting Jia ◽  
Taylor Takasugi ◽  
Eric Smith ◽  
Jayakrishnan Nandakumar ◽  
...  
Keyword(s):  
Telomere Length ◽  
Regulate Telomere Length

scholarly journals Telomere Rapid Deletion Regulates Telomere Length in Arabidopsis thaliana

2006 ◽  
Vol 27 (5) ◽  
pp. 1706-1715 ◽  
Author(s):  
J. Matthew Watson ◽  
Dorothy E. Shippen
Keyword(s):  
Arabidopsis Thaliana ◽  
Telomere Length ◽  
Wild Type ◽  
Telomere Shortening ◽  
Set Point ◽  
Three Generations ◽  
Species Specific ◽  
Regulate Telomere Length

ABSTRACT Telomere length is maintained in species-specific equilibrium primarily through a competition between telomerase-mediated elongation and the loss of terminal DNA through the end-replication problem. Recombinational activities are also capable of both lengthening and shortening telomeres. Here we demonstrate that elongated telomeres in Arabidopsis Ku70 mutants reach a new length set point after three generations. Restoration of wild-type Ku70 in these mutants leads to discrete telomere-shortening events consistent with telomere rapid deletion (TRD). These findings imply that the longer telomere length set point is achieved through competition between overactive telomerase and TRD. Surprisingly, in the absence of telomerase, a subset of elongated telomeres was further lengthened, suggesting that in this background a mechanism of telomerase-independent lengthening of telomeres operates. Unexpectedly, we also found that plants possessing wild-type-length telomeres exhibit TRD when telomerase is inactivated. TRD is stochastic, and all chromosome ends appear to be equally susceptible. The frequency of TRD decreases as telomeres shorten; telomeres less than 2 kb in length are rarely subject to TRD. We conclude that TRD functions as a potent force to regulate telomere length in Arabidopsis.

scholarly journals Seryl tRNA synthetase cooperates with POT1 to regulate telomere length and cellular senescence

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Yingxi Li ◽  
Xiyang Li ◽  
Mei Cao ◽  
Yuke Jiang ◽  
Jie Yan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Telomere Length ◽  
Cellular Senescence ◽  
Direct Interaction ◽  
Causative Factor ◽  
Trna Synthetase ◽  
Dna Repeats ◽  
Telomeric Dna ◽  
Trna Synthetases ◽  
Regulate Telomere Length

AbstractDeregulated telomere length is a causative factor in many physiological and pathological processes, including aging and cancer. Many studies focusing on telomeres have revealed important roles for cooperation between the Shelterin protein complex and telomerase in maintaining telomere length. However, it remains largely unknown whether and how aging-related stresses, such as deregulated protein homeostasis, impact telomere length. Here, we explored the possible roles of aminoacyl tRNA synthetases (AARSs), key enzymes catalyzing the first reactions in protein synthesis, in regulating telomere length and aging. We selected seryl tRNA synthetase (SerRS) since our previous studies discovered expanded functions of SerRS in the nucleus in addition to its canonical cytoplasmic role in protein synthesis. In this study, we revealed that overexpression of SerRS promoted cellular senescence and inhibited the growth of cervical tumor xenografts in mice by triggering the senescence of tumor cells. In the nucleus, SerRS directly bound to telomeric DNA repeats and tethered more POT1 proteins to telomeres through a direct interaction between the UNE-S domain of SerRS and the OB1 domain of POT1. We further demonstrated that SerRS-induced enrichment of POT1 prevented the recruitment of telomerase to telomeres, resulting in progressive telomere shortening. Our data suggested a possible molecular link between protein synthesis and telomere length control, the deregulation of which may be associated with aging and cancer.

scholarly journals The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Evan P Hass ◽  
David C Zappulla
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Telomere Length ◽  
Chromatin Immunoprecipitation ◽  
Telomerase Rna ◽  
Silent Chromatin ◽  
Wild Type ◽  
Yeast Telomerase ◽  
Length Analysis ◽  
Telomere Lengthening ◽  
Regulate Telomere Length

In Saccharomyces cerevisiae and in humans, the telomerase RNA subunit is bound by Ku, a ring-shaped protein heterodimer best known for its function in DNA repair. Ku binding to yeast telomerase RNA promotes telomere lengthening and telomerase recruitment to telomeres, but how this is achieved remains unknown. Using telomere-length analysis and chromatin immunoprecipitation, we show that Sir4 – a previously identified Ku-binding protein that is a component of telomeric silent chromatin – is required for Ku-mediated telomere lengthening and telomerase recruitment. We also find that specifically tethering Sir4 directly to Ku-binding-defective telomerase RNA restores otherwise-shortened telomeres to wild-type length. These findings suggest that Sir4 is the telomere-bound target of Ku-mediated telomerase recruitment and provide one mechanism for how the Sir4-competing Rif1 and Rif2 proteins negatively regulate telomere length in yeast.

Different levels of hypoxia regulate telomere length and telomerase activity

2012 ◽  
Vol 24 (3) ◽  
pp. 213-217 ◽  
Author(s):  
Jing-Zhi Guan ◽  
Wei-Ping Guan ◽  
Toyoki Maeda ◽  
Naoki Makino
Keyword(s):  
Telomere Length ◽  
Telomerase Activity ◽  
Different Levels ◽  
Regulate Telomere Length

scholarly journals Normal mammalian cells negatively regulate telomere length by telomere trimming

2011 ◽  
Vol 20 (23) ◽  
pp. 4684-4692 ◽  
Author(s):  
H. A. Pickett ◽  
J. D. Henson ◽  
A. Y. M. Au ◽  
A. A. Neumann ◽  
R. R. Reddel
Keyword(s):  
Telomere Length ◽  
Mammalian Cells ◽  
Regulate Telomere Length

scholarly journals Counting of Rif1p and Rif2p on Saccharomyces cerevisiae Telomeres Regulates Telomere Length

2004 ◽  
Vol 24 (24) ◽  
pp. 10857-10867 ◽  
Author(s):  
Daniel L. Levy ◽  
Elizabeth H. Blackburn
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Telomere Length ◽  
Pdz Domain ◽  
Protein Oligomerization ◽  
Telomeric Dna ◽  
C Terminus ◽  
Repeat Dna ◽  
Telomere Structure ◽  
Regulate Telomere Length ◽  
Oligomerization Domain

ABSTRACT Telomere length is negatively regulated by proteins of the telomeric DNA-protein complex. Rap1p in Saccharomyces cerevisiae binds the telomeric TG1-3 repeat DNA, and the Rap1p C terminus interacts with Rif1p and Rif2p. We investigated how these three proteins negatively regulate telomere length. We show that direct tethering of each Rif protein to a telomere shortens that telomere proportionally to the number of tethered molecules, similar to previously reported counting of Rap1p. Surprisingly, Rif proteins could also regulate telomere length even when the Rap1p C terminus was absent, and tethered Rap1p counting was completely dependent on the Rif proteins. Thus, Rap1p counting is in fact Rif protein counting. In genetic settings that cause telomeres to be abnormally long, tethering even a single Rif2p molecule was sufficient for maximal effectiveness in preventing the telomere overelongation. We show that a heterologous protein oligomerization domain, the mammalian PDZ domain, when fused to Rap1p can confer telomere length control. We propose that a nucleation and spreading mechanism is involved in forming the higher-order telomere structure that regulates telomere length.

Relationship between telomere length and dyslipidemia in patients with Cushing's syndrome

2013 ◽  
Author(s):  
Anna Aulinas ◽  
Ramirez Maria Jose ◽  
Barahona Maria Jose ◽  
Eugenia Mato ◽  
Olga Bell ◽  
...  
Keyword(s):  
Telomere Length ◽  
Cushing’S Syndrome ◽  
Cushing's Syndrome
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