Global ETD Search
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Showing 1 to 11 of 11 for “"shelterin complex"”.
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Clarifying the Role of the CST Complex in DNA Replication and Repair
… are protected by a number 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 …
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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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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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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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Drivers of melanoma susceptibility
… of telomeres (POT1) gene, a member of the shelterin complex that safeguards telomere integrity, are at high risk for developing melanoma. We successfully described the mechanism by which this happens, showing that the variants identified either disrupt POT1 mRNA splicing or abolish the …
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The Apollo Nuclease Binds To TRF2 and Protects
… of this family of enzymes, hSNM1B/Apollo, in complex with the telomere binding proteins TRF2/Rap1. Due to its low abundance at telomeres, we consider Apollo to be a telomere accessory factor, and not part of the core telomere protein complex, shelterin. Apollo localizes to telomeres by …
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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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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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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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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 …