TY - JOUR. T1 - Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. AU - Mi, Kyung Kim. AU - Mi, Ran Kang. AU - Hyung, Wook Nam. AU - Bae, Young Seuk. AU - Yu, Sam Kim. AU - In, Kwon Chung. PY - 2008/5/16. Y1 - 2008/5/16. N2 - Telomere maintenance is essential for continued cell proliferation and chromosome stability. Telomeres are maintained by telomerase and a collection of associated proteins. The telomeric protein telomeric repeat binding factor 1 (TRF1) negatively regulates telomere length by inhibiting access of telomerase at telomere termini. Here we report that TRF1 interacts with the βsubunit of casein kinase 2 (CK2) and serves as a substrate for CK2. CK2-mediated phosphorylation is required for the efficient telomere binding of TRF1 in vitro and in vivo. Inhibition of CK2 by the CK2 inhibitor 5,6-dichloro-1-β-D- ribofuranosyl-benzimidazole decreased the ability of TRF1 to bind telomeric DNA. The resulting telomere-unbound ...
View mouse Terf2ip Chr8:112011398-112020528 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
TRF1 antibody [3H11] (telomeric repeat binding factor (NIMA-interacting) 1) for ELISA, ICC/IF, WB. Anti-TRF1 mAb (GTX80331) is tested in Human samples. 100% Ab-Assurance.
We have purified a 100 kDa protein, resolved in a Southwestern binding screen of total nuclear proteins from Hela cells with double-stranded human telomeric probe. A polyclonal antiserum raised by this protein recognizes purified nucleolin and stains nucleoli in growing Hela cells. We demonstrate that a truncated form of human nucleolin and a purified deletion derivative of mouse nucleolin bind in vitro to duplex telomeric DNA. This study suggests a new link between telomeres and the nucleolus.. ...
I love writing and blogging! I like looking for information on the latest movies, music and entertainment, celebrity news. Im also working on The Munroe Series - 14 Novels in the Romance, Mystery, Paranormal Category. The Calamity Girl - 2 Novels in Womens Fiction, Mystery, Romance. Young Adult Novels two of them about magic, witches, fairies and giants and I love going to the movies, dancing, socializing with friends and spending time with my loved ones and my dog ...
TY - JOUR. T1 - Solution structure of the arabidopsis thaliana telomeric repeat-binding protein DNA binding domain. T2 - A new fold with an additional C-terminal helix. AU - Sue, Shih Che. AU - Hsiao, Hsin Hao. AU - Chung, Ben C.P.. AU - Cheng, Ying Hsien. AU - Hsueh, Kuang Lung. AU - Chen, Chung Mong. AU - Ho, Chia Hsing. AU - Huang, Tai Huang. PY - 2006/2/10. Y1 - 2006/2/10. N2 - The double-stranded telomeric repeat-binding protein (TRP) AtTRP1 is isolated from Arabidopsis thaliana. Using gel retardation assays, we defined the C-terminal 97 amino acid residues, Gln464 to Val560 (AtTRP1464-560), as the minimal structured telomeric repeat-binding domain. This region contains a typical Myb DNA-binding motif and a C-terminal extension of 40 amino acid residues. The monomeric AtTRP1464-560 binds to a 13-mer DNA duplex containing a single repeat of an A. thaliana telomeric DNA sequence (GGTTTAG) in a 1:1 complex, with a KD∼10-6-10-7 M. Nuclear magnetic resonance (NMR) examination revealed that the ...
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1221 Telomeres lie at the end of chromosomes and contain the repeat sequence 5′-TTAGGG-3′. At the very ends of each telomeric DNA there is a single-stranded, 3′ overhang of between 50 and 500 bases in the G-rich strand, the so-called G-tail. The G-tail length and telomere binding proteins are essential for formation of t-loop and chromosome maintenance. Dominant negative telomere binding protein TRF2 induces the dissociation of TRF2 binding from telomeres and the destruction of t-loop accompanied by G-tail shortening. Recently, we have developed G-tail telomere HPA, a new technique to measure telomeric G-tail (Nature Methods, 2005). This method has the advantage of being simple to perform, accurate and highly sensitive for G-tails as short as 20 nucleotides. In addition, this assay is specific and quantitative for G-tails, and can be used for large-scale screening to understand diseases associated with ageing and telomere dysfunction. Using this assay, we have measured G-tail length in ...
Author Summary Telomeres are protein-DNA structures that protect the ends of eukaryotic chromosomes. A failure in this protective structure can lead to chromosomal instabilities and contribute to cancer and aging. The protective nature of telomeres relies on complex interactions between repetitive telomeric DNA and associated proteins. One major question is how telomeric proteins, including telomere-associated nucleosomes, are modified in order to achieve this protection. In this study, we have discovered that Arabidopsis telomeric nucleosomes contain a unique mixture of both active and inactive chromatin marks. Additionally, the telomeric DNA itself is modified by methylation of cytosines within the telomeric repeat. Regulation of DNA methylation is achieved by telomeric repeat-containing small RNAs, which are derived from the processing of telomeric transcripts by the RNA-dependent DNA methylation pathway. From these data, we infer that the formation of a proper telomere structure is partly regulated
MKVSTLRESSAMASPLPREMEEELVPTGSEPGDTRAKPPVKPKPRALPAKPALPAKPSLLVPVGPRPPRG 1 - 70 PLAELPSARKMNMLAGPQPYGGSKRPLPFAPRPAVEASTGGEATQETGKEEAGKEEPPPLTPPARCAAPG 71 - 140 GVRKAPAPFRPASERFAATTVEEILAKMEQPRKEVLASPDRLWGSRLTFNHDGSSRYGPRTYGTTTAPRD 141 - 210 EDGSTLFRGWSQEGPVKSPAECREEHSKTPEERSLPSDLAFNGDLAKAASSELPADISKPWIPSSPAPSS 211 - 280 ENGGPASPGLPAEASGSGPGSPHLHPPDKSSPCHSQLLEAQTPEASQASPCPAVTPSAPSAALPDEGSRH 281 - 350 TPSPGLPAEGAPEAPRPSSPPPEVLEPHSLDQPPATSPRPLIEVGELLDLTRTFPSGGEEEAKGDAHLRP 351 - 420 TSLVQRRFSEGVLQSPSQDQEKLGGSLAALPQGQGSQLALDRPFGAESNWSLSQSFEWTFPTRPSGLGVW 421 - 490 RLDSPPPSPITEASEAAEAAEAGNLAVSSREEGVSQQGQGAGSAPSGSGSSWVQGDDPSMSLTQKGDGES 491 - 560 QPQFPAVPLEPLPTTEGTPGLPLQQAEERYESQEPLAGQESPLPLATREAALPILEPVLGQEQPAAPDQP 561 - 630 CVLFADAPEPGQALPVEEEAVTLARAETTQARTEAQDLCRASPEPPGPESSSRWLDDLLASPPPSGGGAR 631 - 700 RGAGAELKDTQSPSTCSEGLLGWSQKDLQSEFGITGDPQPSSFSPSSWCQGASQDYGLGGASPRGDPGLG 701 - 770 ERDWTSKYGQGAGEGSTREWASRCGIGQEEMEASSSQDQSKVSAPGVLTAQDRVVGKPAQLGTQRSQEAD 771 - 840 ...
The CDC13 gene has previously been implicated in the maintenance of telomere integrity in Saccharomyces cerevisiae. With the use of two classes of mutations, here it is shown that CDC13 has two discrete roles at the telomere. The cdc13-2est mutation perturbs a function required in vivo for telomerase regulation but not in vitro for enzyme activity, whereas cdc13-1ts defines a separate essential role at the telomere. In vitro, purified Cdc13p binds to single-strand yeast telomeric DNA. Therefore, Cdc13p is a telomere-binding protein required to protect the telomere and mediate access of telomerase to the chromosomal terminus.. ...
POT1 and TPP1 are part of the shelterin complex and are essential for telomere length regulation and maintenance. Naturally occurring mutations of the telomeric POT1-TPP1 complex are implicated in familial glioma, melanoma and chronic lymphocytic leukaemia. Here we report the atomic structure of the interacting portion of the human telomeric POT1-TPP1 complex and suggest how several of these mutations contribute to malignant cancer. The POT1 C-terminus (POT1C) forms a bilobal structure consisting of an OB-fold and a holiday junction resolvase domain. TPP1 consists of several loops and helices involved in extensive interactions with POT1C. Biochemical data shows that several of the cancer-associated mutations, partially disrupt the POT1-TPP1 complex, which affects its ability to bind telomeric DNA efficiently. A defective POT1-TPP1 complex leads to longer and fragile telomeres, which in turn promotes genomic instability and cancer.. ...
The ends of eukaryotic chromosomes are capped by telomeres which consist of tandem G-rich DNA repeats stabilized by the shelterin protein complex. Telomeres shorten progressively in most normal cells due to the end replication problem. In more than 85% of cancers however, the telomere length is maintained by telomerase; a reverse transcriptase that adds telomeric TTAGGG repeats using its integral RNA template. The strong association between telomerase activity and malignancy in many cancers suggests that telomerase activity could serve as a diagnostic marker. We demonstrate single-molecule, real-time telomerase extension activity observed digitally as the telomeric repeats are added to a substrate. The human telomerase complex pulled down from mammalian cells displays extension activity dependent on dNTP concentration. In complex with the processivity factor, POT1-TPP1, telomerase adds repeats at an accelerated rate and yields longer products. Our assay provides a unique detection platform that ...
We studied the expression of four telomere-associated proteins (TRF1, TRF2, POT1, and RAP1 genes) in normal and tumor tissues of lung cancer patients and observed significant down-regulation of TRF1 in tumor samples and no significant difference in expression between tumor and normal tissues for TRF2, POT1, and RAP1 (Table 3). The down-regulation of TRF1 in tumor tissue was consistent when we used GAPDH alone, 18S rRNA alone, β-actin alone (data not shown) or the geometric mean of three genes as internal control. In previous published studies, controversial data were presented for these telomeric genes in cancer. Some studies suggested that TRF1 and TRF2 were down-regulated in tumor tissues (21-26), whereas others showed that TRF1 or TRF2 was up-regulated (27-30). Different tumor type and tumor stage may account for some of these differences. One study showed that tumor stage and telomere length might also influence POT1 expression in cancer (31). Their data indicated that in stage I/II gastric ...
Pinx1 - Pinx1 (untagged) - Mouse PIN2/TERF1 interacting, telomerase inhibitor 1 (Pinx1), (10ug) available for purchase from OriGene - Your Gene Company.
Binding affinity to MDMX (unknown origin) assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF ...
Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5-TTAGGG-3 repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5-TTAGGG-3 sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B
Telomeres, the complex of repetitive DNA and associated proteins at chromosome ends, are essential for chromosome stability. They prevent chromosome ends from fusing and from being recognized as damaged DNA. The telomeres from several organisms have been shown to be located at the nuclear periphery. Transcriptional repression and heterochromatin formation are other processes intimately associated with telomeres and assigned to functional subdomains within the nucleus (reviewed in Greider, 1996; Cockell and Gasser, 1999). Telomeric DNA generally consists of tandemly repeated, short G‐rich sequences and ends with a 3′ overhang, formed by the degradation of the ultimate primer used for synthesizing the lagging strand during DNA replication (reviewed in de Lange, 1995). It was recently observed that telomeres in mammalian cells, ciliates and trypanosomes end with large T loops (for telomere loops), presumably formed by invasion of the 3′ telomeric overhang into the duplex telomeric repeat ...
The involvement of TRF2 and the shelterin complex in telomere protection and maintenance has been extensively studied in telomerase-positive tumor cell lines. However, the role of TRF2 in ALT cells has not been investigated in depth. For this reason, we used a number of approaches, ranging from RNAi to functional inhibition, to manipulate TRF2 function in ALT cells. Colony formation experiments clearly show that RNAi-mediated TRF2 knockdown results in a marked decrease in the number of colonies, thus implicating an effect on either apoptosis or cell cycle, or both. Nevertheless, we find that apoptosis is not induced in TRF2-depleted cells or in cells expressing the dominant-negative ΔBΔM mutant in transient, and only moderately in stable settings. In a previous study, the ALT cell line SAOS2 was shown to be resistant to the cytotoxic effects of TRF2 inactivation, and this was ascribed to the absence of p53 (Karlseder et al., 1999). However, we show here that U2OS cells, which, unlike SAOS2, ...
Human telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex required for the protection and replication of chromosome ends.
Figure 3. Mutations in STN1 result in abnormal telomere phenotypes. (A) DNA samples, prepared from PBLs of patient P1, her heterozygous father (F1), and a noncarrier sibling (S1) and patient P2, his heterozygous mother (M2), and two independent control samples (C), were analyzed by in-gel hybridization. Duplicated lanes were electrophoresed in the same gel, and then separated and hybridized to a G-rich or C-rich telomeric probe, as indicated above the panels. After native hybridization to detect single-stranded telomeric DNA (top), the gels were denatured and rehybridized with the same probes to detect the overall duplex telomeric DNA (bottom). Treatment with exonuclease I is indicated above the lanes. (B) Graphic illustration of the mean telomere length for the patients and their family members, calculated based on the following number of independent measurements of four in-gels and two Southern analyses: P1:6, M1:3, F1:3, S1:3, P2:9, M2:3, F2:1, C1:2, and C2:3. (C) Graphic illustration of the ...
We were interested in characterizing proteins involved in telomere-membrane interactions in human sperm. To this end, nuclear membranes were partially solubilized by treatment with 0.5% Triton X-100 in buffer containing 100 mM NaCl. Earlier FISH data (Zalensky et al. 1995) demonstrated that such treatment destroyed association of human sperm telomeres with nuclear membrane. Usual methods for telomere-binding protein isolation involve nuclei extraction with salt buffers of higher molarity (e.g., 0.6 M KCl). Surprisingly, a Triton extract of human sperm was active in binding ds(TTAGGG) DNA, and this telomere-binding activity appeared to be identical to hSTBP previously described in 0.5 M NaCl nuclear extracts (Zalensky et al. 1997) as judged by a characteristic gel-retardation pattern (Fig. 1 a). The pretreatment of crude Triton-soluble hSTBP (hSTBPTR) with 6 M Urea, DNAase, and RNAase does not influence ds(TTAGGG) binding, at the same time activity is sensitive to temperature, and destroyed by ...
Stable telomeres play a key role to the survival of cancer cells; therefore, different cancer chemotherapeutic approaches have been developed in order to disrupt or destabilise telomeres or telomerase. One of the newest methods is the disruption of vital protein-protein interactions in the telomere, such as that between shelterin components TRF1 and TIN2. The principal aim of this project was to obtain a novel peptide-like molecule, an analogue of a key interacting region of TIN2 that could compete effectively for the binding sites on TRF1 and so lead to the destabilisation of telomere structure. Molecular modelling and simulations were undertaken as the starting point of the project. Structure-based drug design was applied, starting from the available crystal structure data. A library of peptide analogues of the TRF1-binding motif in TIN2 was designed using the MM-GBSA simulation method to predict binding affinities. Then, a number of the peptide analogues were selected from the library for ...
ZBTB48 binds through the last of its 11 zinc fingers directly to telomeric DNA (TTAGGG, in red) as well as subtelomeric variant repeats (TTGGG/TCAGGG, grey), which represent the protective caps at the end of chromosomes. In addition, it binds to the promoter sequences (dark blue) of specific target genes including mitochondrial fission process 1, MTFP1. In the absence of ZBTB48 (right panel) telomeres become longer whereas the expression of ZBTB48 target genes is strongly reduced. For instance, ZBTB48 KO (knock-out) cells loose the expression of MTFP1 leading to defects in the mitochondrial network with mitochondria clustering around the nucleus instead of being widely spread throughout the cell.
Cover: Conservative DNA replication of telomeres in human cells that rely on alternative lengthening of telomeres (ALT) to escape replicative senescence. Telomere strand-specific fluorescence in situ hybridization (FISH), performed in three consecutive steps (denaturing FISH/non-denaturing chromosome orientation FISH/denaturing FISH), distinguishes between semiconservative and conservative telomeric replication. Images from the second (left) and third (right) staining steps show a chromosome (circled) with a telomeric end that is conservatively replicated (green, G-rich telomeric repeats; red, C-rich telomeric repeats; blue, DAPI). From Fani-Marlen Roumelioti, Sotirios K Sotiriou, Thanos D Halazonetis, Sarantis Gagos and colleagues: Alternative lengthening of human telomeres is a conservative DNA replication process with features of break-induced replication. For detail, see Scientific Report on page 1731. ...
1PGZ: Structure-based incorporation of 6-methyl-8-(2-deoxy-beta-ribofuranosyl)isoxanthopteridine into the human telomeric repeat DNA as a probe for UP1 binding and destabilization of G-tetrad structures
J Ye, C Lenain, S Bauwens, A Rizzo, A Saint-Léger, A Poulet, D Benarroch, F Magdinier, J Morere, S Amiard, E Verhoeyen,S Britton, P Calsou, B Salles, A Bizard, M Nadal, E Salvati, L Sabatier, Y Wu, A Biroccio, A Londoño-Vallejo, MJ Giraud-Panis and E Gilson* (2010) TRF2 and Apollo cooperate with Topoisomerase 2a to protect human telomeres from replicative damage, Cell, 142: 230-242; IF= 32, ...
POT1 is one of the six core components of the human telomeric protein complex (reviewed in de Lange, 2005). This complex is composed of TRF1, TRF2, TIN2, TPP1 (previously known as PIP1, PTOP, or TINT1), Rap1, and POT1, which are thought to fulfill the two main functions of telomeres: the recruitment and regulation of telomerase, and the protection of chromosome ends. Defects in telomere protection activate the DNA damage response, leading to a DNA damage signal and inappropriate DNA repair reactions at chromosome ends. The cell cycle arrest resulting from telomere dysfunction is thought to be responsible for the finite lifespan of human cells lacking telomerase.. The current challenge is to understand how the telomeric complex protects chromosome ends from being recognized as sites of DNA damage. One approach is to define which repair and signaling pathways are repressed at natural chromosome ends by studying the events at dysfunctional telomeres. This approach has shown that chromosome ends are ...
Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere ...
We measured the effects of long-term NRTI and NNRTI exposure on telomere length maintenance using the HT29 human colorectal adenocarcinoma cell model (Table 2). HT29 has robust telomerase activities, as measured by the PCR-based telomerase activity assay [31]. HT29 cells were treated with a minimum of two concentrations of NRTIs or NNRTIs. Cell proliferation and growth rate was monitored continuously. Long-term treatment of HT29 cells with AZT is known to cause telomere length attrition [9,10,11,13]. Using the terminal restriction fragment (TRF) assay, we confirmed substantial inhibitory effects of AZT on telomere length maintenance in HT29 cells (Figure 6A and 6B). Mean telomere length was determined as a weighted average with reference to DNA standards. Figure 7. Continuous treatment of HT29 cells with the adenosine analogs TDF and ddI causes observable telomere shortening. A. TRF blots of untreated (left), TDF-treated (right) HT29 cells. PDL at which TRF was analyzed is shown above each lane. ...
Dr. de Langes lab studies telomeres, protective elements at the ends of chromosomes critical for the stability and maintenance of the genetic information. Deficiency in telomere function can cause genomic alterations found in cancer, and the gradual loss of telomeres contributes to aging of human cells. Dr. de Lange seeks to understand how telomere protection is established and what happens when telomere function is lost during the early stages of tumor formation. Dr. de Langes lab focuses on mammalian telomeres, which are made up of long arrays of double-stranded TTAGGG repeats that end in a single-stranded 3′ overhang. These telomeric repeats wither away in a shortening process that is associated with cell proliferation. Telomerase can counteract this attrition and stabilizes telomeres by adding back telomeric repeats. However, telomerase is absent from most human somatic cells, and, as a result, cells eventually die due to depletion of their telomere reserve. Cancer cells, on the other ...
Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT-PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative ...
Human telomeres associate with shelterin, a six-protein complex that protects chromosome ends from being recognized as sites of DNA damage. The shelterin subunit TRF2 (telomeric repeat-binding factor 2) protects telomeres by facilitating their organization into the protective capping structure. We have reported previously that the DNA-PKcs (DNA-dependent protein kinase catalytic subunit)-interacting protein KIP associates with telomerase through an interaction with hTERT (human telomerase...
The protective caps on chromosome ends - known as telomeres - consist of DNA and associated proteins that are essential for chromosome integrity. A fundamental part of ensuring proper telomere function is maintaining adequate length of the telomeric DNA tract. Telomeric repeat sequences are synthesized by the telomerase reverse transcriptase, and, as such, telomerase is a central player in the maintenance of steady-state telomere length. Evidence from both yeast and mammals suggests that telomere-associated proteins positively or negatively control access of telomerase to the chromosome terminus. In yeast, positive regulation of telomerase access appears to be achieved through recruitment of the enzyme by the end-binding protein Cdc13p. In contrast, duplex-DNA-binding proteins assembled along the telomeric tract exert a feedback system that negatively modulates telomere length by limiting the action of telomerase. In mammalian cells, and perhaps also in yeast, binding of these proteins probably ...
Previous work from the de Lange lab showed that TRF2, a shelterin protein that binds to the duplex part of the telomere, is crucial for telomere protection. Without TRF2, telomeres activate a DNA damage signal and are repaired by the same pathways that act on DNA breaks. TRF2 brings a second shelterin protein, POT1, to the telomeres. Because POT1 binds to single-stranded telomeric DNA present at the very end of the chromosomes, the de Lange lab asked how POT1 contributes to the protection of telomeres.. "We had previously removed TRF2 from mouse cells and seen many dramatic phenotypes," says de Lange, "all of the telomeres ligate together; there is a massive DNA damage response and the cells basically die. We argued that if the function of TRF2 was to bring POT1 to the DNA, then we should observe the same phenotype if we removed POT1.". To determine if this was the case, graduate student Dirk Hockemeyer, the first author of the paper, decided to remove the POT1 gene from mice. Humans have one ...
Yeast telomeric DNA is assembled into a nonnucleosomal chromatin structure known as the telosome, which is thought to influence the transcriptional repression of genes placed in its vicinity, a phenomenon called telomere position effect (TPE). The product of the RAP1 gene, Rap1p, is a component of the telosome. We show that the fraction of cells exhibiting TPE can be substantially reduced by expressing large amounts of a deletion derivative of Rap1p that is unable to bind DNA, called Rap1 delta BBp, or by introducing extra telomeres on a linear plasmid, presumably because both compete in trans with telomeric chromatin for factor(s) important for TPE. This reduction in TPE, observed in three different strains, was demonstrated for two different genes, each assayed at a different telomere. In contrast, the addition of internal tracts of telomeric DNA on a circular plasmid had very little effect on TPE. The product of the SIR3 gene, Sir3p, appears to be limiting for TPE. Overexpression of Sir3p ...
Studies revealed that NBS1 plays important roles in maintaining genome stability, but the underlying mechanism is controversial and elusive. Our study using clinical samples showed that NBS1 was involved in ATM/ATR-dependent pathways. NBS1 deficiency severely affected the phosphorylation of ATM/ATR as well as their downstream targets. The inefficiency in activating ATM/ATR-dependent pathways led to multiple defects in cellular responses towards DNA damage, such as inefficiency in inhibiting DNA synthesis and resistance to DNA-damaging agent. Accelerated telomere shortening was also observed in NBS fibroblasts, consistent with an earlier onset of cellular replicative senescence in vitro. This abnormality may be due to the shelterin protein TRF2 which was found upregulated in NBS fibroblasts. Prevalent telomeric fusions and cellular aneuploidy were also observed in NBS fibroblasts. Collectively, our study suggests a possible mechanism that NBS1 deficiency simultaneously affects ATM/ATR-dependent ...
This gene encodes a protein that is involved in telomere function. This protein is one of six core proteins in the telosome/shelterin telomeric complex, which functions to maintain telomere length and to protect telomere ends. Through its interaction with other components, this protein plays a key role in the assembly and stabilization of this complex, and it mediates the access of telomerase to the telomere. Multiple transcript variants encoding different isoforms have been found for this gene. This gene, which is also referred to as TPP1, is distinct from the unrelated TPP1 gene on chromosome 11, which encodes tripeptidyl-peptidase I. [provided by RefSeq, Jul 2008 ...
In the new paper published in Nature Communications, the group of Gian Paolo Dotto describes the central role of CSL in telomere homeostasis of dermal fibroblasts with important implications for genomic instability of cancer stromal cells
Telomeres are regions of tandem arrays of TTAGGG repeats and associated proteins located at chromosomal ends that allow cells to distinguish chromosome ends from double-strand breaks and protect chromosomes from end-to-end fusion, recombination and degradation (Houben et al., 2008). Telomeres are not linear structures, telomeric DNA is maintained in a loop structure due to many key proteins. This structure serves to protect the ends of chromosomes (Neidle and Parkinson 2003).Telomeres are subjected to shortening at each cycle of cell division due to incomplete synthesis of the lagging strand during DNA replication owing to the inability of DNA polymerase to completely replicate the ends of chromosome DNA (end-replication problem) (Muraki et al., 2012). Therefore, they assume to limit the number of cell cycles and act as a mitotic clock (Olovnikov, 1996). Shortened telomeres cause decreased proliferative potential, thus triggering senescence (Blackburn et al., 2006).Telomere length (TL) is highly
Telomeres are repeat (TTAGGG) n sequences that form terminal ends of chromosomes and have several functions, such as protecting the coding DNA from erosion at mitosis. Due to chromosomal rearrangements through evolutionary history (e.g., inversions and fusions), telomeric sequences are also found between the centromere and the terminal ends (i.e., at interstitial telomeric sites, ITSs). ITS telomere sequences have been implicated in heritable disease caused by genomic instability of ITS...
Telomeres belong to the key functional elements of eukaryotic chromosomes. Like all the other parts of the genome, they exist and function as complexes of DNA with histones and various nonhistone proteins, including specific telomere-binding proteins.
Telomeres usually contain some version of tandem copies of sequences like 5-CCCCAA-3 on one strand and 5-TTGGGG on the complementary strand. The GT-rich strand comprises the 3-end and **sticks out** longer than the CA strand (and forms a loop, sealing the end). Specifically for human telomeres, there are 300-8,000 sets of repeats of the sequence CCCTAA /TTAGGG, then a 100-200 nucleotide extension of single-stranded TTAGGG repeats, hence the comment that telomeres have high GT content. But why? The best way to understand this beautiful system is to watch the very simple but very revealing short animation in the link above called telomere animation of how telomerase works at the telomere (see especially step 5 and later). Note that it is all about the requirements of polymerase for a free 3 -OH (and a ss DNA template strand)! It might also help to scan quickly through the very good article from Nature Network listed above as well ...
Telomeres usually contain some version of tandem copies of sequences like 5-CCCCAA-3 on one strand and 5-TTGGGG on the complementary strand. The GT-rich strand comprises the 3-end and **sticks out** longer than the CA strand (and forms a loop, sealing the end). Specifically for human telomeres, there are 300-8,000 sets of repeats of the sequence CCCTAA /TTAGGG, then a 100-200 nucleotide extension of single-stranded TTAGGG repeats, hence the comment that telomeres have high GT content. But why? The best way to understand this beautiful system is to watch the very simple but very revealing short animation in the link above called telomere animation of how telomerase works at the telomere (see especially step 5 and later). Note that it is all about the requirements of polymerase for a free 3 -OH (and a ss DNA template strand)! It might also help to scan quickly through the very good article from Nature Network listed above as well ...
Complete information for ACD gene (Protein Coding), ACD, Shelterin Complex Subunit And Telomerase Recruitment Factor, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Chronic damage or injury to nerves causes changes in the primary sensory neurons located in the dorsal root ganglion (DRG) and in their central connections.
what happens if you ligate a huge telmore onto a DNA, like some ridiculously long sequence? would the DNA be able to divide for an excessive amount of time? what happens if you ligate a telomere from one species onto DNA from another species? does the new telomere still help the cell live longer? hazel p.s. why is this message cross-posted to alt.binaries.nospam.panties? now theres a difficult scientific problem ...