Global ETD Search
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Showing 1 to 20 of 23 for “"shelterin"”.
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Testing the T-loop Model of Telomeric End Protection
… thought to accomplish this through the action of shelterin. Shelterin is a multi-protein complex where each subunit is dedicated to a specific role in repressing a form of DNA damage signaling, repair, or recruiting telomerase to extend the telomere end. One of the critical anchor points of …
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Investigating Mechanisms of Telomere End-Protection
<p>Shelterin is an essential telomeric protein complex that prevents DNA damage signaling and DNA repair in a compartmentalized manner. We assessed contributions of the conserved shelterin component, Rap1, to telomere endprotection. Rap1 was first discovered in budding yeast as a transcription …
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Biochemical and structural studies of human telomerase regulation
… telomerase is recruited to telomeres by the shelterin component TPP1 (Nandakumar et al., 2012; Sexton et al., 2012; Zhong et al., 2012), which forms a heterodimer with another shelterin component POT1 (Xin et al., 2007). After synthesizing approximately 60 telomeric repeats, telomerase is …
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On the Second Telomere Maintenance Machine: Structure, Recruitment, and Regulation of the CST–Polα/primase C-strand Fill-in Complex
… DNA is recognized and bound by the six-subunit shelterin complex, which plays critical roles in telomere protection and maintenance. First, shelterin protects the genome by repressing aberrant activation of the DNA damage response at telomeres, which resemble broken DNA ends. Second, due to …
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Pathways of NHEJ at Dysfunctional Telomeres and Their Resolution
<p>Shelterin is a multiprotein complex that prevents DNA damage signaling at chromosome ends. In its absence, DNA repair pathways are activated that can promote the fusion of dysfunctional telomeres resulting in chromosomal instability. The work presented here aims to understand how telomeres are …
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Mechanisms of Telomere End Protection by TRF2
<p>Shelterin is a six-subunit protein complex that protects the ends of mammalian chromosomes, called telomeres. The six subunits of shelterin, TRF1, TRF2, TIN2, TPP1, POT1, and Rap1, each have distinct roles in telomere homeostasis. These include telomere length regulation and preventing telomeres …
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Clarifying the Role of the CST Complex in DNA Replication and Repair
… of essential protein complexes including the shelterin complex and CST (CTC1 – STN1 – TEN1) complex. CST is an RPA-like ssDNA binding protein that is vital for telomere length maintenance via inhibition of telomerase and stimulation of DNA polymerase α -primase during C-strand fill-in …
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Further Insight into the Two Functions of Telomeres: Determining the Role of Tankyrase1 in Telomere Length Regulation and Tin2 in Telomere Protection
… to telomeres through its interaction with the shelterin component TRF1. Tankyrase1 poly(ADP-ribosyl)ates TRF1 in vitro, and its nuclear overexpression leads to loss of TRF1 and telomere elongation, suggesting that tankyrase1 is a positive regulator of telomere length. In agreement with this …
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A Novel Phosphorylation Site in the Telomeric Protein TRF2 is Regulated by the ATR Kinase and Plays a Role in Relieving Replication Stress at the Telomere
… specific functions. We report that the human shelterin component, TRF2, overexpressed in 293T cells, is phosphorylated on serine 368 (S368) in a caffeine and wortmannin sensitive manner. Phosphorylation is induced by hydroxyurea (HU) and ultraviolet (UV) radiation but not Ionizing Radiation …
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Mechanisms That Ensure the Proper Terminal Structure of Mammalian Telomeres
… responses at telomeres, through the deletion of shelterin components, had no apparent effect on the chromatin organization of telomeres and did not cause overt eviction of nucleosomes from the telomere terminus. Next, I identified a role for the shelterin-associated Apollo nuclease in generating …
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Effect of oxidative stress on human telomeric DNA structural dynamics and accessibility
… binding of the protection of telomeres 1 (POT1) shelterin protein, suggesting enhanced accessibility of telomeric DNA to interacting molecules. The increased dynamics and accessibility caused by 8OG is comparable to the effect of a base substitution from G to C at the same position, which …
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MULTI-ORGAN FAILURE DRIVEN BY TELOMERE UNCAPPING
The telomere-bound shelterin complex safeguards chromosome ends from being recognized as DNA double-strand breaks, a function mostly dependent on TRF2. Loss of TRF2 results in telomere uncapping, activation of the DNA damage response, and chromosomal end-to-end fusions, with dramatic consequences …
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The Apollo Nuclease Binds To TRF2 and Protects
… not part of the core telomere protein complex, shelterin. Apollo localizes to telomeres by interacting directly with the TRFH domain of TRF2. Structural analysis of this interaction revealed an interface in the TRFH domain of TRF2 that is predicted to be shared by numerous accessory factors …
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Genetic and Molecular Studies of Endometrial Cancer
… inactivating Pot1a, a key component of the shelterin complex that stabilizes telomeres in endometrial epithelium. Inactivation of Pot1a by itself does not stimulate endometrial carcinogenesis. However, simultaneous inactivation of Pot1a and p53 results in endometrial intraepithelial …
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53BP1/Shieldin Counteract DSB Resection Through Fill-In Synthesis
… of telomeres lacking end protection from the shelterin component TRF2, and facilitates end-joining at programmed breaks generated during class switch recombination in the immune system. The role of 53BP1 in double strand break (DSB) repair outside of these three well-studied contexts is less …
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Replicative Senescence is ATM-Driven, Reversible, and Delayed by Reduced ATM Activity at Low Oxygen
… critically-short telomeres, despite unaltered shelterin expression. Instead, this greater tolerance of short telomeres is due to a diminished ability of ATM to respond to DSBs, despite normal expression of ATM pathway components. Our data is consistent with hypoxia-induced sequestration of ATM …
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Modeling Sporadic Tumor Formation Driven By Telomere Dysfunction In The Gastrointestinal Tract
… null mice to achieve critically short telomeres. Shelterin is a complex of six core proteins that bind to telomeres specifically. Pot1a is a highly conserved member of this complex that specifically binds to the telomeric single-stranded 3’ G-rich overhang. Previous work in our lab has shown that …
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Mechanistic Understanding of the Role of TRF1 in Telomere Replication
… telomeres are hard to replicate, and the shelterin subunit TRF1 is important for facilitating the replication of telomeric DNA. Deletion of TRF1 results in several phenotypes that are thought to be associated with telomere replication stress, including ATR signaling, fork stalling, sister …
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Neotelomere Formation by Telomerase in Human Cells
… breaks (DSBs), which humans accomplish with the shelterin complex. The reverse transcriptase telomerase counteracts the shortening of telomeres that occurs with cell division due to incomplete DNA replication and nucleolytic resection. During human development, the expression of the reverse …
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Role of ORCA/LRWD1 in the maintenance of telomere integrity
… to ssDNA. I identified that the SUMOylation of shelterin components in essential for ORCA recruitment to ALT-telomeres. The loss of ORCA in ALT-positive cells elevates the levels of two mediators of Homologous Recombination (HR), RPA and RAD51, and consistent with this, we observe increased …
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