POT1-TPP1 telomere length regulation and disease

Aramburu, Tomas M.; Plucinsky, Sarah M.; Skordalakes, Emmanuel

doi:10.1016/j.csbj.2020.06.040

Cited by 38 publications

(38 citation statements)

References 115 publications

(159 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These tandem repeats are bound by the shelterin complex, which is composed of six proteins: telomere repeat factor 1 and 2 (TRF1, TRF2), protection of telomeres 1 (POT1), TRF1-interacting nuclear protein 2 (TIN2), tripeptidyl peptidase I (TPP1), and repressor/activator protein 1 (RAP1) ( Figure 1 ) ( 2 ). The Shelterin complex plays a fundamental role in protecting chromosome ends and in telomere length regulation ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

TERT—Regulation and Roles in Cancer Formation

et al. 2020

View full text Add to dashboard Cite

Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase. Telomerase complex plays a key role in cancer formation by telomere dependent or independent mechanisms. Telomere maintenance mechanisms include complex TERT changes such as gene amplifications, TERT structural variants, TERT promoter germline and somatic mutations, TERT epigenetic changes, and alternative lengthening of telomere. All of them are cancer specific at tissue histotype and at single cell level. TERT expression is regulated in tumors via multiple genetic and epigenetic alterations which affect telomerase activity. Telomerase activity via TERT expression has an impact on telomere length and can be a useful marker in diagnosis and prognosis of various cancers and a new therapy approach. In this review we want to highlight the main roles of TERT in different mechanisms of cancer development and regulation.

show abstract

Section: Introductionmentioning

confidence: 99%

TERT—Regulation and Roles in Cancer Formation

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Pal et al ( 40 ) analysed the gene expression profiles of RAP1 and POT1 in 65 samples of RCC tumour and adjacent normal renal parenchymal tissues. The RAP1 mRNA expression was found to be significantly increased with the grade and subtype of RCC, whereas POT1 expression levels were upregulated in tumour tissues compared with the corresponding normal renal tissues, but POT1 expression was not associated with grades, stages and subtypes of RCC ( 33 , 39 ).…”

Section: Rccmentioning

confidence: 91%

“…Repressor-activator protein 1 (RAP1) and protection of telomeres protein 1 (POT1) are essential members of the shelterin complex, the expression of which is crucial for telomere maintenance ( 3 , 39 ). Pal et al ( 40 ) analysed the gene expression profiles of RAP1 and POT1 in 65 samples of RCC tumour and adjacent normal renal parenchymal tissues.…”

Section: Rccmentioning

confidence: 99%

Roles of telomeres and telomerase in age‑related renal diseases (Review)

Wang

et al. 2020

Mol Med Rep

View full text Add to dashboard Cite

age-related renal diseases, which account for various progressive renal disorders associated with cellular and organismal senescence, are becoming a substantial public health burden. However, their aetiologies are complicated and their pathogeneses remain poorly understood. Telomeres and telomerase are known to be essential for maintaining the integrity and stability of eukaryotic genomes and serve crucial roles in numerous related signalling pathways that activate renal functions, such as repair and regeneration. Previous studies have reported that telomere dysfunction served a role in various types of age-related kidney disease through various different molecular pathways. The present review aimed to summarise the current knowledge of the association between telomeres and ageing-related kidney diseases and explored the contribution of dysfunctional telomeres to these diseases. The findings may help to provide novel strategies for treating patients with renal disease. Contents 1. introduction 2. Structural renal changes induced by ageing 3. rcc 4. ageing-associated cKd 5. Kidney fibrosis 6. aKi 7. renal cysts 8. conclusion

show abstract

“…The TPP1-POT1 complex suppresses the ATR-dependent DNA damage response, and helps recruit telomerase to telomeres for DNA replication [6]. The role of the TPP1-POT1 heterodimer is complex and multifaceted [5][6][7]. The heterodimer can inhibit telomerase binding as part of the shelterin complex, or can serve as a processivity factor for telomerase during telomere extension [8].…”

Section: Introductionmentioning

confidence: 99%

“…POT1 is anchored to the shelterin complex by its interaction with the protein TPP1 [5]. The TPP1-POT1 complex suppresses the ATR-dependent DNA damage response, and helps recruit telomerase to telomeres for DNA replication [6]. The role of the TPP1-POT1 heterodimer is complex and multifaceted [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

POT1 Stability and Binding Measured by Fluorescence Thermal Shift Assays

DeLeeuw

Monsen

Petrauskas

et al. 2021

Preprint

View full text Add to dashboard Cite

The protein POT1 (Protection of Telomeres 1) is an integral part of the shelterin complex that protects the ends of human chromosomes from degradation or end fusions. It is the only component of shelterin that binds single-stranded DNA. We describe here the application of two separate fluorescent thermal shift assays (FTSA) that provide quantitative biophysical characterization of POT1 stability and its interactions. The first assay uses Sypro Orange™ and monitors the thermal stability of POT1 and its binding under a variety of conditions. This assay is useful for the quality control of POT1 preparations, for biophysical characterization of its DNA binding and, potentially, as an efficient screening tool for binding of small molecule drug candidates. The second assay uses a FRET-labeled human telomeric G-quadruplex structure that reveals the effects of POT1 binding on thermal stability from the DNA frame of reference. These complementary assays provide efficient biophysical approaches for the quantitative characterization of multiple aspects of POT1 structure and function. The results from these assays provide thermodynamics details of POT1 folding, the sequence selectivity of its DNA binding and the thermodynamic profile for its binding to its preferred DNA binding sequence. Most significantly, results from these assays elucidate two mechanisms for the inhibition of POT1 – DNA interactions. The first is by competitive inhibition at the POT1 DNA binding site. The second is indirect and is by stabilization of G-quadruplex formation within the normal POT1 single-stranded DNA sequence to prevent POT1 binding.

show abstract

POT1-TPP1 telomere length regulation and disease

Cited by 38 publications

References 115 publications

TERT—Regulation and Roles in Cancer Formation

TERT—Regulation and Roles in Cancer Formation

Roles of telomeres and telomerase in age‑related renal diseases (Review)

POT1 Stability and Binding Measured by Fluorescence Thermal Shift Assays

Contact Info

Product

Resources

About