LIVIVO - Search results -

Search results

Result 1 - 10 of total 24

Search options

Article ; Online: A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice.

Frescas, David / de Lange, Titia

2014 Volume 28, Issue 2, Page(s) 153–166

Abstract: The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the ... ...

Abstract	The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations affect telomere function, we generated mice with the equivalent of the TIN2 K280E DC allele (TIN2(DC)) by gene targeting. Whereas homozygous TIN2(DC/DC) mice were not viable, first-generation TIN2(+/DC) mice were healthy and fertile. In the second and third generations, the TIN2(+/DC) mice developed mild pancytopenia, consistent with hematopoietic dysfunction in DC, as well as diminished fecundity. Bone marrow telomeres of TIN2(+/DC) mice shortened over the generations, and immortalized TIN2(+/DC) mouse embryonic fibroblasts (MEFs) showed telomere shortening with proliferation. Unexpectedly, telomere shortening was accelerated in TIN2(+/DC) mTR(-/-) mice and MEFs compared with TIN2(+/+) mTR(-/-) controls, establishing that the TIN2(DC) telomere maintenance defect was not solely due to diminished telomerase action. The TIN2(DC) allele induced mild ATR kinase signaling at telomeres and a fragile telomere phenotype, suggestive of telomere replication problems. These data suggest that this TIN2-DC mutation could induce telomeric dysfunction phenotypes in telomerase-negative somatic cells and tissues that further exacerbate the telomere maintenance problems in telomerase-positive stem cell compartments.
MeSH term(s)	Animals ; Cell Line, Tumor ; Disease Models, Animal ; Dyskeratosis Congenita/genetics ; Fertility/genetics ; Gene Knock-In Techniques ; HeLa Cells ; Humans ; Mice ; Mutation ; Pancytopenia/genetics ; Signal Transduction ; Telomerase/metabolism ; Telomere/pathology ; Telomere Shortening/genetics ; Telomere-Binding Proteins/genetics
Chemical Substances	Telomere-Binding Proteins ; Tinf2 protein, mouse ; Telomerase (EC 2.7.7.49)
Language	English
Publishing date	2014-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.233395.113
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 54: Show issues

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: TRF2-tethered TIN2 can mediate telomere protection by TPP1/POT1.

Frescas, David / de Lange, Titia

Molecular and cellular biology

2014 Volume 34, Issue 7, Page(s) 1349–1362

Abstract: The shelterin protein TIN2 is required for the telomeric accumulation of TPP1/POT1 heterodimers and for the protection of telomeres by the POT1 proteins (POT1a and POT1b in the mouse). TIN2 also binds to TRF1 and TRF2, improving the telomeric ... ...

Abstract	The shelterin protein TIN2 is required for the telomeric accumulation of TPP1/POT1 heterodimers and for the protection of telomeres by the POT1 proteins (POT1a and POT1b in the mouse). TIN2 also binds to TRF1 and TRF2, improving the telomeric localization of TRF2 and its function. Here, we ask whether TIN2 needs to interact with both TRF1 and TRF2 to mediate the telomere protection afforded by TRF2 and POT1a/b. Using a TIN2 allele deficient in TRF1 binding (TIN2-L247E), we demonstrate that TRF1 is required for optimal recruitment of TIN2 to telomeres and document phenotypes associated with the TIN2-L247E allele that are explained by insufficient TIN2 loading onto telomeres. To bypass the requirement for TRF1-dependent recruitment, we fused TIN2-L247E to the TRF2-interacting (RCT) domain of Rap1. The RCT-TIN2-L247E fusion showed improved telomeric localization and was fully functional in terms of chromosome end protection by TRF2, TPP1/POT1a, and TPP1/POT1b. These data indicate that when sufficient TIN2 is loaded onto telomeres, its interaction with TRF1 is not required to mediate the function of TRF2 and the TPP1/POT1 heterodimers. We therefore conclude that shelterin can protect chromosome ends as a TRF2-tethered TIN2/TPP1/POT1 complex that lacks a physical connection to TRF1.
MeSH term(s)	Animals ; Cells, Cultured ; DNA-Binding Proteins/metabolism ; Mice ; Mutagenesis, Site-Directed ; Protein Binding ; Protein Interaction Domains and Motifs ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Shelterin Complex ; Telomere/genetics ; Telomere/metabolism ; Telomere Homeostasis/genetics ; Telomere Homeostasis/physiology ; Telomere-Binding Proteins/deficiency ; Telomere-Binding Proteins/genetics ; Telomere-Binding Proteins/metabolism ; Telomeric Repeat Binding Protein 1/chemistry ; Telomeric Repeat Binding Protein 1/genetics ; Telomeric Repeat Binding Protein 1/metabolism ; Telomeric Repeat Binding Protein 2/chemistry ; Telomeric Repeat Binding Protein 2/genetics ; Telomeric Repeat Binding Protein 2/metabolism
Chemical Substances	Acd protein, mouse ; DNA-Binding Proteins ; POT1 protein, mouse ; Recombinant Fusion Proteins ; Shelterin Complex ; TRF2 protein, mouse ; Telomere-Binding Proteins ; Telomeric Repeat Binding Protein 1 ; Telomeric Repeat Binding Protein 2 ; Tinf2 protein, mouse
Language	English
Publishing date	2014-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.01052-13
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Binding of TPP1 protein to TIN2 protein is required for POT1a,b protein-mediated telomere protection.

Frescas, David / de Lange, Titia

The Journal of biological chemistry

2014 Volume 289, Issue 35, Page(s) 24180–24187

Abstract: The single-stranded DNA binding proteins in mouse shelterin, POT1a and POT1b, accumulate at telomeres as heterodimers with TPP1, which binds TIN2 and thus links the TPP1/POT1 dimers with TRF1 and TRF2/Rap1. When TPP1 is tethered to TIN2/TRF1/TRF2, POT1a ... ...

Abstract	The single-stranded DNA binding proteins in mouse shelterin, POT1a and POT1b, accumulate at telomeres as heterodimers with TPP1, which binds TIN2 and thus links the TPP1/POT1 dimers with TRF1 and TRF2/Rap1. When TPP1 is tethered to TIN2/TRF1/TRF2, POT1a is thought to block replication protein A binding to the single-stranded telomeric DNA and prevent ataxia telangiectasia and Rad3-related kinase activation. Similarly, TPP1/POT1b tethered to TIN2 can control the formation of the correct single-stranded telomeric overhang. Consistent with this view, the telomeric phenotypes following deletion of POT1a,b or TPP1 are phenocopied in TIN2-deficient cells. However, the loading of TRF1 and TRF2/Rap1 is additionally compromised in TIN2 KO cells, leading to added phenotypes. Therefore, it could not be excluded that, in addition to TIN2, other components of shelterin contribute to the recruitment of TPP1/POT1a,b as suggested by previous reports. To test whether TIN2 is the sole link between TPP1/POT1a,b and telomeres, we defined the TPP1 interaction domain of TIN2 and generated a TIN2 allele that was unable to interact with TPP1 but retained its interaction with TRF1 and TRF2. We demonstrated that cells expressing TIN2ΔTPP1 instead of wild-type TIN2 phenocopy the POT1a,b knockout setting without showing additional phenotypes. Therefore, these results are consistent with TIN2 being the only mechanism by which TPP1/POT1 heterodimers bind to shelterin and function in telomere protection.
MeSH term(s)	Alleles ; Amino Acid Sequence ; Animals ; Cell Line, Transformed ; DNA-Binding Proteins/physiology ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Serine Proteases/chemistry ; Serine Proteases/metabolism ; Shelterin Complex ; Telomerase/metabolism ; Telomere Homeostasis ; Telomere-Binding Proteins/chemistry ; Telomere-Binding Proteins/genetics ; Telomere-Binding Proteins/metabolism
Chemical Substances	Acd protein, mouse ; DNA-Binding Proteins ; POT1 protein, mouse ; POT1b protein, mouse ; Shelterin Complex ; Telomere-Binding Proteins ; Tinf2 protein, mouse ; Telomerase (EC 2.7.7.49) ; Serine Proteases (EC 3.4.-)
Language	English
Publishing date	2014-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M114.592592
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: TRF2-Tethered TIN2 Can Mediate Telomere Protection by TPP1/POT1

Frescas, David / De Lange, Titia

Molecular and Cellular Biology. 2014 Apr. 1, v. 34, no. 7 p.1349-1362

2014

Abstract	The shelterin protein TIN2 is required for the telomeric accumulation of TPP1/POT1 heterodimers and for the protection of telomeres by the POT1 proteins (POT1a and POT1b in the mouse). TIN2 also binds to TRF1 and TRF2, improving the telomeric localization of TRF2 and its function. Here, we ask whether TIN2 needs to interact with both TRF1 and TRF2 to mediate the telomere protection afforded by TRF2 and POT1a/b. Using a TIN2 allele deficient in TRF1 binding (TIN2-L247E), we demonstrate that TRF1 is required for optimal recruitment of TIN2 to telomeres and document phenotypes associated with the TIN2-L247E allele that are explained by insufficient TIN2 loading onto telomeres. To bypass the requirement for TRF1-dependent recruitment, we fused TIN2-L247E to the TRF2-interacting (RCT) domain of Rap1. The RCT-TIN2-L247E fusion showed improved telomeric localization and was fully functional in terms of chromosome end protection by TRF2, TPP1/POT1a, and TPP1/POT1b. These data indicate that when sufficient TIN2 is loaded onto telomeres, its interaction with TRF1 is not required to mediate the function of TRF2 and the TPP1/POT1 heterodimers. We therefore conclude that shelterin can protect chromosome ends as a TRF2-tethered TIN2/TPP1/POT1 complex that lacks a physical connection to TRF1.
Keywords	alleles ; mice ; telomeres
Language	English
Dates of publication	2014-0401
Size	p. 1349-1362.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.01052-13
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Utilization of TALEN and CRISPR/Cas9 technologies for gene targeting and modification.

Pu, Jiali / Frescas, David / Zhang, Baorong / Feng, Jian

Experimental biology and medicine (Maywood, N.J.)

2015 Volume 240, Issue 8, Page(s) 1065–1070

Abstract: The capability to modify the genome precisely and efficiently offers an extremely useful tool for biomedical research. Recent developments in genome editing technologies such as transcription activator-like effector nuclease and the clustered regularly ... ...

Abstract	The capability to modify the genome precisely and efficiently offers an extremely useful tool for biomedical research. Recent developments in genome editing technologies such as transcription activator-like effector nuclease and the clustered regularly interspaced short palindromic repeats system have made genome modification available for a number of organisms with relative ease. Here, we introduce these genome editing techniques, compare and contrast each technical approach and discuss their potential to study the underlying mechanisms of human disease using patient-derived induced pluripotent stem cells.
MeSH term(s)	Animals ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Targeting/methods ; Genome, Human ; Humans ; Induced Pluripotent Stem Cells
Language	English
Publishing date	2015-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/1535370215584932
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.111: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Telomere Protection by TPP1/POT1 Requires Tethering to TIN2.

Takai, Kaori K / Kibe, Tatsuya / Donigian, Jill R / Frescas, David / de Lange, Titia

Molecular cell

2017 Volume 67, Issue 1, Page(s) 162

Language	English
Publishing date	2017-06-28
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2017.05.033
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5055: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer.

Frescas, David / Pagano, Michele

Nature reviews. Cancer

2008 Volume 8, Issue 6, Page(s) 438–449

Abstract: The maintenance and preservation of distinct phases during the cell cycle is a highly complex and coordinated process. It is regulated by phosphorylation--through the activity of cyclin-dependent kinases (CDKs)--and protein degradation, which occurs ... ...

Abstract	The maintenance and preservation of distinct phases during the cell cycle is a highly complex and coordinated process. It is regulated by phosphorylation--through the activity of cyclin-dependent kinases (CDKs)--and protein degradation, which occurs through ubiquitin ligases such as SCF (SKP1-CUL1-F-box protein) complexes and APC/C (anaphase-promoting complex/cyclosome). Here, we explore the functionality and biology of the F-box proteins, SKP2 (S-phase kinase-associated protein 2) and beta-TrCP (beta-transducin repeat-containing protein), which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates.
MeSH term(s)	Animals ; Apoptosis Regulatory Proteins/metabolism ; Cell Cycle Proteins/physiology ; Co-Repressor Proteins ; Cullin Proteins/physiology ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Cyclin-Dependent Kinases/metabolism ; DNA-Binding Proteins/metabolism ; Forkhead Box Protein O1 ; Forkhead Transcription Factors/metabolism ; Humans ; NF-kappa B/metabolism ; Neoplasm Proteins/metabolism ; Neoplasms/metabolism ; Nerve Tissue Proteins/metabolism ; Oncogenes ; RNA-Binding Proteins/metabolism ; Repressor Proteins/metabolism ; S-Phase Kinase-Associated Proteins/physiology ; SKP Cullin F-Box Protein Ligases/physiology ; beta-Transducin Repeat-Containing Proteins/physiology ; cdc25 Phosphatases/metabolism
Chemical Substances	Apoptosis Regulatory Proteins ; Cell Cycle Proteins ; Co-Repressor Proteins ; Cullin 1 ; Cullin Proteins ; DNA-Binding Proteins ; FOXO1 protein, human ; Forkhead Box Protein O1 ; Forkhead Transcription Factors ; NF-kappa B ; Neoplasm Proteins ; Nerve Tissue Proteins ; PDCD4 protein, human ; RCOR1 protein, human ; RNA-Binding Proteins ; Repressor Proteins ; S-Phase Kinase-Associated Proteins ; beta-Transducin Repeat-Containing Proteins ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; SKP Cullin F-Box Protein Ligases (EC 2.3.2.27) ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; CDC25A protein, human (EC 3.1.3.48) ; cdc25 Phosphatases (EC 3.1.3.48)
Language	English
Publishing date	2008-06-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/nrc2396
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 24: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Immune checkpoint protein VSIG4 as a biomarker of aging in murine adipose tissue.

Hall, Brandon M / Gleiberman, Anatoli S / Strom, Evguenia / Krasnov, Peter A / Frescas, David / Vujcic, Slavoljub / Leontieva, Olga V / Antoch, Marina P / Kogan, Valeria / Koman, Igor E / Zhu, Yi / Tchkonia, Tamara / Kirkland, James L / Chernova, Olga B / Gudkov, Andrei V

Aging cell

2020 Volume 19, Issue 10, Page(s) e13219

Abstract: Adipose tissue is recognized as a major source of systemic inflammation with age, driving age-related tissue dysfunction and pathogenesis. Macrophages (Mφ) are central to these changes yet adipose tissue Mφ (ATMs) from aged mice remain poorly ... ...

Abstract	Adipose tissue is recognized as a major source of systemic inflammation with age, driving age-related tissue dysfunction and pathogenesis. Macrophages (Mφ) are central to these changes yet adipose tissue Mφ (ATMs) from aged mice remain poorly characterized. To identify biomarkers underlying changes in aged adipose tissue, we performed an unbiased RNA-seq analysis of ATMs from young (8-week-old) and healthy aged (80-week-old) mice. One of the genes identified, V-set immunoglobulin-domain-containing 4 (VSIG4/CRIg), encodes a Mφ-associated complement receptor and B7 family-related immune checkpoint protein. Here, we demonstrate that Vsig4 expression is highly upregulated with age in perigonadal white adipose tissue (gWAT) in two mouse strains (inbred C57BL/6J and outbred NIH Swiss) independent of gender. The accumulation of VSIG4 was mainly attributed to a fourfold increase in the proportion of VSIG4
MeSH term(s)	Adipose Tissue, White/metabolism ; Aging/metabolism ; Animals ; Biomarkers/metabolism ; Female ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Complement/metabolism
Chemical Substances	Biomarkers ; Receptors, Complement ; VSIG4 protein, mouse
Language	English
Publishing date	2020-08-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.13219
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6581: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Murine mesenchymal cells that express elevated levels of the CDK inhibitor p16(Ink4a) in vivo are not necessarily senescent.

Frescas, David / Hall, Brandon M / Strom, Evguenia / Virtuoso, Lauren P / Gupta, Mahima / Gleiberman, Anatoli S / Rydkina, Elena / Balan, Vitaly / Vujcic, Slavoljub / Chernova, Olga B / Gudkov, Andrei V

Cell cycle (Georgetown, Tex.)

2017 Volume 16, Issue 16, Page(s) 1526–1533

Abstract: Age-related health decline has been attributed to the accumulation of senescent cells recognized in vivo by p16(Ink4a) expression. The pharmacological elimination of p16(Ink4a)-positive cells from the tissues of mice was shown to extend a healthy ... ...

Abstract	Age-related health decline has been attributed to the accumulation of senescent cells recognized in vivo by p16(Ink4a) expression. The pharmacological elimination of p16(Ink4a)-positive cells from the tissues of mice was shown to extend a healthy lifespan. Here, we describe a population of mesenchymal cells isolated from mice that are highly p16(INK4a)-positive are proficient in proliferation but lack other properties of cellular senescence. These data, along with earlier reports on p16(Ink4a)-positive macrophages, indicate that p16(Ink4a)-positive and senescent cell populations only partially intersect, therefore, extending the list of potential cellular targets for anti- aging therapies.
MeSH term(s)	Animals ; Cell Proliferation ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Humans ; Leukocyte Common Antigens/metabolism ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Mice, Inbred C57BL
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2017-06-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2017.1339850
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5881: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Telomere protection by TPP1/POT1 requires tethering to TIN2.

Takai, Kaori K / Kibe, Tatsuya / Donigian, Jill R / Frescas, David / de Lange, Titia

Molecular cell

2011 Volume 44, Issue 4, Page(s) 647–659

Abstract: To prevent ATR activation, telomeres deploy the single-stranded DNA binding activity of TPP1/POT1a. POT1a blocks the binding of RPA to telomeres, suggesting that ATR is repressed through RPA exclusion. However, comparison of the DNA binding affinities ... ...

Abstract	To prevent ATR activation, telomeres deploy the single-stranded DNA binding activity of TPP1/POT1a. POT1a blocks the binding of RPA to telomeres, suggesting that ATR is repressed through RPA exclusion. However, comparison of the DNA binding affinities and abundance of TPP1/POT1a and RPA indicates that TPP1/POT1a by itself is unlikely to exclude RPA. We therefore analyzed the central shelterin protein TIN2, which links TPP1/POT1a (and POT1b) to TRF1 and TRF2 on the double-stranded telomeric DNA. Upon TIN2 deletion, telomeres lost TPP1/POT1a, accumulated RPA, elicited an ATR signal, and showed all other phenotypes of POT1a/b deletion. TIN2 also affected the TRF2-dependent repression of ATM kinase signaling but not to TRF2-mediated inhibition of telomere fusions. Thus, while TIN2 has a minor contribution to the repression of ATM by TRF2, its major role is to stabilize TPP1/POT1a on the ss telomeric DNA, thereby allowing effective exclusion of RPA and repression of ATR signaling.
MeSH term(s)	Animals ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; DNA Damage ; DNA Repair ; DNA, Single-Stranded/chemistry ; DNA, Single-Stranded/genetics ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression ; HeLa Cells ; Humans ; Mice ; Mice, Knockout ; Protein Binding/genetics ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Shelterin Complex ; Signal Transduction/genetics ; Telomere/metabolism ; Telomere-Binding Proteins/genetics ; Telomere-Binding Proteins/metabolism ; Telomeric Repeat Binding Protein 2/genetics ; Telomeric Repeat Binding Protein 2/metabolism
Chemical Substances	ACD protein, human ; Acd protein, mouse ; Cell Cycle Proteins ; DNA, Single-Stranded ; DNA-Binding Proteins ; POT1 protein, mouse ; Recombinant Proteins ; Shelterin Complex ; Telomere-Binding Proteins ; Telomeric Repeat Binding Protein 2 ; Tinf2 protein, mouse ; ATR protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1)
Language	English
Publishing date	2011-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2011.08.043
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5055: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito