Journal ArticleDOI
Tankyrase, a Poly(ADP-Ribose) Polymerase at Human Telomeres
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TLDR
Tankyrase, a protein with homology to ankyrins and to the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP), was identified and localized to human telomeres.Abstract:
Tankyrase, a protein with homology to ankyrins and to the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP), was identified and localized to human telomeres. Tankyrase binds to the telomeric protein TRF1 (telomeric repeat binding factor-1), a negative regulator of telomere length maintenance. Like ankyrins, tankyrase contains 24 ankyrin repeats in a domain responsible for its interaction with TRF1. Recombinant tankyrase was found to have PARP activity in vitro, with both TRF1 and tankyrase functioning as acceptors for adenosine diphosphate (ADP)-ribosylation. ADP-ribosylation of TRF1 diminished its ability to bind to telomeric DNA in vitro, suggesting that telomere function in human cells is regulated by poly(ADP-ribosyl)ation.read more
Citations
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Shelterin: the protein complex that shapes and safeguards human telomeres
TL;DR: The current data argue that shelterin is emerging as a protein complex with DNA remodeling activity that acts together with several associated DNA repair factors to change the structure of the telomeric DNA, thereby protecting chromosome ends.
Journal ArticleDOI
Mammalian Telomeres End in a Large Duplex Loop
Jack D. Griffith,Laurey Comeau,Soraya Rosenfield,Rachel M. Stansel,Alessandro Bianchi,Heidi Moss,Titia de Lange +6 more
TL;DR: Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro, which may provide a general mechanism for the protection and replication of telomeres.
Journal ArticleDOI
Switching and Signaling at the Telomere
TL;DR: The structure of telomeres, the protective DNA-protein complexes at eukaryotic chromosomal ends, and several molecular mechanisms involved in telomere functions are described.
Journal ArticleDOI
Poly(ADP-ribose): novel functions for an old molecule.
TL;DR: The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD+, is a unique post-translational modification that regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated.
Journal ArticleDOI
Poly(adp-ribosyl)ation reactions in the regulation of nuclear functions
TL;DR: The total dependence of poly(ADP-ribose) synthesis on DNA strand breaks strongly suggests that this post-translational modification is involved in the metabolism of nucleic acids, and the presence of PARP in these multiprotein complexes clearly supports an important role for poly(ADE-ribosyl)ation reactions in DNA transactions.
References
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Journal ArticleDOI
TRF2 Protects Human Telomeres from End-to-End Fusions
TL;DR: It is shown that the human telomeric protein TRF2 plays a key role in the protective activity of telomeres, and the results raise the possibility that chromosome end fusions and senescence in primary human cells may be caused by loss byTRF2 from shortenedtelomeres.
Journal ArticleDOI
Control of telomere length by the human telomeric protein TRF1.
B van Steensel,T de Lange +1 more
TL;DR: It is proposed that the binding of TRF1 controls telomere length in cis by inhibiting the action of telomerase at the ends of individual telomeres, and shown that the human telomeric-repeat binding factor TRF 1 is involved in this regulation.
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Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2.
TL;DR: TRF2 as discussed by the authors is a distant homologue of TRF1 that carries a very similar Myb-related DNA-binding motif and was found to have similar DNA binding activity and domain organization, but its N terminus was basic rather than acidic.
Journal ArticleDOI
Poly(adp-ribose) polymerase : a molecular nick-sensor
TL;DR: Poly(ADP-ribose) polymerase (PARP) participates in the intricate network of systems developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents.
Journal ArticleDOI
A Human Telomeric Protein
Laura Chong,Bas van Steensel,Dominique Broccoli,Hediye Erdjument-Bromage,John Hanish,Paul Tempst,Titia de Lange +6 more
TL;DR: Immunofluorescent labeling shows that TRF specifically colocalizes with telomeric DNA in human interphase cells and is located at chromosome ends during metaphase, demonstrating that human telomeres form a specialized nucleoprotein complex.