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Raj K Pandita - One of the best experts on this subject based on the ideXlab platform.
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abstract 2250 role of single strand Binding Protein 1 in tert recruitment to telomeres and in maintaining telomere g overhangs
Cancer Research, 2014Co-Authors: Tej K Pandita, Raj K PanditaAbstract:Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Telomeres cap the ends of all eukaryotic chromosomes from degradation or end-to-end fusions. Mammalian telomeres are maintained by telomerase which is a ribonucleoProtein complex that includes a reverse transcriptase catalytic unit called TERT and a functional telomerase RNA (TR or TERC), which acts as a template to maintain telomere length. Telomerase maintains telomere length, by overcoming incomplete lagging strand synthesis known as the “end replication problem” during DNA replication. Mammalian stem and cancer cells utilize telomerase to extend telomeric G-overhangs to partially (stem cells) or completely (tumor cells) maintain telomere ends. Cells expressing telomerase also have higher levels of single strand Binding 1 (SSB1) Protein, which has a known critical role in the DNA damage responses and double strand break repair specifically by homologous recombination. We have established that SSB1 binds specifically to G-strand telomeric DNA in vitro, and associates in vivo with telomeres both in human and mouse cell lines. Interestingly, SSB1 interacts with the TERT Protein, and determines the amount of TERT interaction with telomeres. Deletion/depletion of SSB1 reduces TERT interaction with telomeres and leads to G-overhang loss, but has no effect on in vitro telomerase activity. We will discuss, how SSB1 is required for telomerase recruitment to telomeres to facilitate G-strand DNA extension and to maintain telomeres. Citation Format: Tej K. Pandita, Raj Pandita. Role of single strand Binding Protein 1 in TERT recruitment to telomeres and in maintaining telomere G-overhangs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2250. doi:10.1158/1538-7445.AM2014-2250
Susan M Gasser - One of the best experts on this subject based on the ideXlab platform.
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the shelterin Protein pot 1 anchors caenorhabditis elegans telomeres through sun 1 at the nuclear periphery
Journal of Cell Biology, 2013Co-Authors: Helder Ferreira, Benjamin D Towbin, Thibaud Jegou, Susan M GasserAbstract:Telomeres are specialized Protein-DNA structures that protect chromosome ends. In budding yeast, telomeres form clusters at the nuclear periphery. By imaging telomeres in embryos of the metazoan Caenorhabditis elegans, we found that telomeres clustered only in strains that had activated an alternative telomere maintenance pathway (ALT). Moreover, as in yeast, the unclustered telomeres in wild-type embryos were located near the nuclear envelope (NE). This bias for perinuclear localization increased during embryogenesis and persisted in differentiated cells. Telomere position in early embryos required the NE Protein SUN-1, the Single-Strand Binding Protein POT-1, and the small ubiquitin-like modifier (SUMO) ligase GEI-17. However, in postmitotic larval cells, none of these factors individually were required for telomere anchoring, which suggests that additional mechanisms anchor in late development. Importantly, targeted POT-1 was sufficient to anchor chromatin to the NE in a SUN-1-dependent manner, arguing that its effect at telomeres is direct. This high-resolution description of telomere position within C. elegans extends our understanding of telomere organization in eukaryotes.
Stephen C West - One of the best experts on this subject based on the ideXlab platform.
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dna repair synthesis facilitates rad52 mediated second end capture during dsb repair
Molecular Cell, 2008Co-Authors: Michael J Mcilwraith, Stephen C WestAbstract:Homologous recombination (HR) is essential for the repair of DNA double-strand breaks (DSBs) in mitotic and meiotic cells. HR occurs through a series of steps involving DSB resection, invasion of Single-Stranded DNA into homologous duplex DNA to form a D loop, repair synthesis, and second-end capture. We show that DNA repair synthesis, catalyzed by human DNA polymerase eta (poleta) acting upon the priming strand of a D loop, leads to capture and annealing of the second end of a resected DSB in reactions mediated by RAD52 Protein. Second-end capture products were not detected when poleta was replaced by other polymerases such as poldelta or poliota. RAD52 could not be replaced by RAD51. We also found that the RAD52-dependent reaction was stimulated by the Single-Strand Binding Protein RPA, but not by E. coli SSB. Following repair synthesis and second-end capture, de novo DNA synthesis was observed from the captured second DNA end.
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bypass of dna heterologies during ruvab mediated three and four strand branch migration
Journal of Molecular Biology, 1996Co-Authors: David E Adams, Stephen C WestAbstract:Abstract During general genetic recombination and recombinational DNA repair, DNA damages and heterologies are often encountered which must be efficiently processed by the cellular recombination machinery. In RecA-mediated three-strand exchange reactions between Single-Stranded circular and linear duplex DNA, or four-strand exchange reactions between gapped circular and linear duplex DNA, heterologies can only be bypassed in vitro when they are short in length and are followed by homologous DNA downstream. Larger DNA inserts block RecA-mediated strand exchange, indicating that effective bypass requires other components of the recombination machinery. The RuvA and RuvB Proteins of Escherichia coli form an important part of this machinery. In this work, we have analysed the ability of RuvA and RuvB to bypass large tracts of DNA heterology in both three- and four-strand exchange reactions, using recombination intermediates made by the E. coli RecA Protein. Under optimal reaction conditions for RuvAB, up to 1000 bp of DNA heterology can by bypassed in three-strand reactions and 300 bp of DNA heterology can be bypassed in four-strand reactions. Whereas high concentrations of RuvB (in the absence of RuvA) can promote homologous branch migration, we find that RuvB alone is unable to catalyse heterologous bypass, indicating an essential role for both Proteins in homologous recombination and recombinational DNA repair processes. Under certain conditions, the bypass of heterology is stimulated by the Single-Strand Binding Protein SSB.
Tej K Pandita - One of the best experts on this subject based on the ideXlab platform.
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abstract 2250 role of single strand Binding Protein 1 in tert recruitment to telomeres and in maintaining telomere g overhangs
Cancer Research, 2014Co-Authors: Tej K Pandita, Raj K PanditaAbstract:Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Telomeres cap the ends of all eukaryotic chromosomes from degradation or end-to-end fusions. Mammalian telomeres are maintained by telomerase which is a ribonucleoProtein complex that includes a reverse transcriptase catalytic unit called TERT and a functional telomerase RNA (TR or TERC), which acts as a template to maintain telomere length. Telomerase maintains telomere length, by overcoming incomplete lagging strand synthesis known as the “end replication problem” during DNA replication. Mammalian stem and cancer cells utilize telomerase to extend telomeric G-overhangs to partially (stem cells) or completely (tumor cells) maintain telomere ends. Cells expressing telomerase also have higher levels of single strand Binding 1 (SSB1) Protein, which has a known critical role in the DNA damage responses and double strand break repair specifically by homologous recombination. We have established that SSB1 binds specifically to G-strand telomeric DNA in vitro, and associates in vivo with telomeres both in human and mouse cell lines. Interestingly, SSB1 interacts with the TERT Protein, and determines the amount of TERT interaction with telomeres. Deletion/depletion of SSB1 reduces TERT interaction with telomeres and leads to G-overhang loss, but has no effect on in vitro telomerase activity. We will discuss, how SSB1 is required for telomerase recruitment to telomeres to facilitate G-strand DNA extension and to maintain telomeres. Citation Format: Tej K. Pandita, Raj Pandita. Role of single strand Binding Protein 1 in TERT recruitment to telomeres and in maintaining telomere G-overhangs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2250. doi:10.1158/1538-7445.AM2014-2250
Weihong Tan - One of the best experts on this subject based on the ideXlab platform.
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carbon nanotubes protect dna strands during cellular delivery
ACS Nano, 2008Co-Authors: Joseph A Phillips, Haipeng Liu, Ronghua Yang, Weihong TanAbstract:To protect against nuclease digestion, or Single-Strand Binding Protein interactions, oligonucleotides for targeted delivery into intracellular systems must be stable. To accomplish this, we have developed single-walled carbon nanotubes as a carrier for Single-Stranded DNA probe delivery. This has resulted in superior biostability for intracellular application and, hence, has achieved the desired protective attributes, which are particularly important when DNA probes are used for intracellular measurements. Specifically, when bound to single-walled carbon nanotubes, DNA probes are protected from enzymatic cleavage and interference from nucleic acid Binding Proteins. Moreover, and equally important, our study shows that a single-walled carbon nanotube-modified DNA probe, which targets a specific mRNA inside living cells, has increased self-delivery capability and intracellular biostability when compared to free DNA probes. Therefore, this new conjugate provides significant advantages for basic genomic stud...