Disease relevance of TTTY4C

• PIK3CG was mapped by fluorescence in situ hybridization adjacent and telomeric to a commonly deleted segment defined previously in myeloid leukemias with breakpoints within 7q22 [1].
• Recent findings revealed that the structure of the amplicon differs interindividually and that coamplification of genes in telomeric proximity to MYCN might play a relevant role in neuroblastoma development and response to treatment, respectively [2].
• Haplotype-specific gene expression profiles in a telomeric major histocompatibility complex gene cluster and susceptibility to autoimmune diseases [3].
• We examined the expression of telomeric DNA in 21 atypical adenomatous hyperplasias (AAHs) and 40 bronchioloalveolar carcinomas (BACs) measuring 2 cm or less in greatest diameter using fluorescent in situ hybridization and the expression of human telomerase reverse transcriptase (hTERT) messenger RNA (mRNA) in 35 AAHs and 37 BACs [4].
• The patients with severe RSTS all had deletions comprising telomeric neighbor genes of CREBBP, including DNASE1, a dominant gene encoding a nuclease that has been associated with systemic lupus erythematodes [5].

Psychiatry related information on TTTY4C

• Recently, VCXA, which is located approximately 0.7Mb telomeric to the STS gene, was reported as a candidate gene for mental retardation (MR) in patients with XLI [6].

High impact information on TTTY4C

• Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres [7].
• A ribosomal DNA promoter replacing the promoter of a telomeric VSG gene expression site can be efficiently switched on and off in T. brucei [8].
• Chromosome stability requires a dynamic balance of DNA loss and gain in each terminal tract of telomeric repeats [9].
• To determine the consequences of telomere dysfunction in noncycling cells, we used conditional deletion of the telomeric protein TRF2 in hepatocytes [10].
• Reconstitution of telomeric DNA at each cell division implies the coordination of DNA semiconservative replication with several processing events still poorly understood [11].

Biological context of TTTY4C

• Overexpression of a mutant Pot1b allele that cannot bind telomeric DNA initiated a DNA damage response at telomeres that led to p53-dependent senescence [12].
• Surprisingly, this 'deprotection' of the shortened telomeres does not result in increased exonucleolytic degradation, but in a higher proportion of anaphase bridges containing telomeric repeats in atrad50/tert plants, compared to tert mutant plants [13].
• T. brucei has >1000 VSG genes and pseudogenes, of which one is transcribed at a time from one of multiple telomeric VSG expression sites [14].
• POT1 (protection of telomere 1) is a highly conserved single-stranded telomeric binding protein that is essential for telomere end protection [12].
• These results suggest that SWNTs might have the intriguing potential to modulate human telomeric DNA structures in vivo, like biologically relevant B-A and B-Z DNA transitions, which is of great interest for drug design and cancer therapy [15].

Anatomical context of TTTY4C

• By the use of quantitative telomere-length measurements, we demonstrate severe telomeric shortening in both Hus1-deficient mouse embryonic fibroblasts and thymocytes from conditional Hus1-knockout mice [16].
• A comparative analysis of bleomycin-induced incomplete chromosome elements in two mammalian cell lines using a telomeric PNA probe [17].
• Telomere activity of lymphocytes was measured by telomeric-repeat amplification protocol [18].
• Immortalization of normal human cytotrophoblast cells by reconstitution of telomeric reverse transcriptase activity [19].
• The effect of HIV-1 on telomerase activity, certain regulators, and telomeric terminal restriction fragment length on lymphoid Jurkat cells was used in measuring the proliferative activity of T lymphoid cells before and after being infected [20].

Associations of TTTY4C with chemical compounds

• The arrested cells have a 4N DNA content, and addition of caffeine causes immediate entry into mitosis, suggesting a G(2) arrest due to an ATM- and/or ATR-mediated checkpoint. gammaH2AX accumulates at telomeres, indicating a telomeric DNA damage response, the likely cause of the checkpoint [21].
• We conclude that Apollo is a novel component of the human telomeric complex and works together with TRF2 to protect chromosome termini from being recognized and processed as DNA damage [22].
• The potential interaction of daidzin, an ingredient of soy isoflavones, with human telomeric antiparallel G-quadruplex dAG(3)(T(2)AG(3))(3) was studied using ESI-MS, PAGE, CD and molecular simulation [23].
• Interactions of the human telomeric DNA with terbium-amino acid complexes [24].
• The question arises whether platination of quadruplex structures of human telomeric sequences by cisplatin could be relevant from a biological point of view [25].

Analytical, diagnostic and therapeutic context of TTTY4C

• In the current study, we used a combination of gel electrophoresis, circular dichroism, and UV melting analysis to investigate the structure and stability of G-quadruplexes formed by long telomeric DNAs from Oxytricha and human, where the length of the repeat (n) = 4 to 12 [26].
• Binding of the telomerase ribonucleoprotein from the ciliate Euplotes aediculatus to telomeric DNA in vitro has been examined by electron microscopy (EM) [27].
• Gel filtration confirmed that purified E. aediculatus telomerase is an active dimer in solution, and comparison of the size of the DNA-associated complex with apoferritin suggests that E. aediculatus telomerase binds to a single telomeric 3'-end as a dimer [27].
• Quantitative PCR was performed in some biopsies to determine the ratio of the testis-specific transcript DDX3Yt1 to the total DDX3Y transcription [28].
• Estimation of binding constants for complexes of polyamides and human telomeric DNA sequences by electrospray ionization mass spectrometry [29].

References