| Telomeres are short nucleotide sequences found at the end of linear chromosomes which protect the genetic information. In vertebrates, telomeres have the hexameric sequence TTAGGG. Show During DNA replication, the double stranded DNA is unwound and DNA polymerase synthesizes new strands. However, as DNA polymerase moves in a unidirectional manner (from 5’ to 3’), only the leading strand can be replicated continuously. In the case of the lagging strand, DNA replication is discontinuous. In humans small RNA primers attach to the lagging strand DNA, and the DNA is synthesized in small stretches of about 100-200 nucleotides, which are termed Okazaki fragments [1][2]. The RNA primers are removed, replaced with DNA and the Okazaki fragments ligated together. At the end of the lagging strand, it is impossible to attach an RNA primer, meaning that there will be a small amount of DNA lost each time the cell divides. This ‘end replication problem’ has serious consequences for the cell as it means the DNA sequence cannot be replicated correctly, with the loss of genetic information. In order to prevent this, telomeres are repeated hundreds to thousands of times at the end of the chromosomes. Each time cell division occurs, a small section of telomeric sequences are lost to the end replication problem, thereby protecting the genetic information. At some point, the telomeres become critically short. This attrition leads to cell senescence, where the cell is unable to divide, or apoptotic cell death. Telomeres are the basis for the Hayflick limit, the number of times a cell is able to divide before reaching senescence [3].  Telomeres are located at the end of chromosomes, where they help protect against loss of DNA during replication. Telomeres can be restored by the enzyme telomerase, which extends telomeres length. Telomerase activity is found in cells that undergo regular division, such as stem cells and lymphocyte cells of the immune system. Telomeres can also be extended through the Alternative Lengthening of Telomeres (ALT) pathway. In this case, rather than being extended, telomeres are switched between chromosomes by homologous recombination. As a result of the telomere swap, one set of daughter cells will have shorter telomeres, and the other set will have longer telomeres. While still not fully understood, the ALT pathway is reviewed in [4]. A downside to telomere extension is the potential for uncontrolled cell division and cancer. Abnormally high telomerase activity has been found in the majority [5][6] of cancer cells, and non-telomerase tumours often exhibit ALT pathway activation. As well as the potential for losing genetic information, cells with short telomeres are at a high risk for improper chromosome recombination, which can lead to genetic instability and aneuploidy (an abnormal number of chromosomes). Cellular geometry plays an important role in nuclear architecture and chromosome dynamics, including telomeres [7]. Recent work has shown that mechanical forces can regulate pathways involved in maintenance of genome integrity. ATR is a nuclear protein which can sense DNA damage. Upon osmotic stress or mechanical stretching, ATR relocalises to the nuclear membrane, suggesting that ATR is mechanosensitive, and this property helps it protect the DNA from mechanical stresses [8]. Furthermore, stretching of the telomere tetraplex structure by magnetic tweezers has shown that it exists in three distinct, folded states that have different lifetimes and mechanical stability [9]. These findings suggest that mechanical forces influence the role of telomeres in protecting the genome and in tumourgenesis [10]. × More Questions FAQ
How is DNA packed inside the nucleus?Sruthi Jagannathan2018-01-17T12:47:16+08:30 How is DNA packed inside the nucleus? A series of processes must take place that enable the cell to package DNA within the confines of the nucleus whilst retaining its ability to transcribe and duplicate the entire DNA sequence and maintain its integrity. This is achieved through an elaborate process of DNA condensation that sees DNA packaged into 46 chromosomes (or 23 chromosome pairs) in humans. Read more.. How is translation terminated?Sruthi Jagannathan2017-12-19T16:53:50+08:30 How is translation terminated? The next step in the process of translation is termination. In this step an mRNA stop codon indicates that no additional amino acids are to be added to the growing protein. Read more.. How are ribosomes recycled during translation?Sruthi Jagannathan2017-12-19T16:50:22+08:30 How are ribosomes recycled during translation? The final step in translation is ribosome recycling, which sees the ribosome split into its smaller subunit parts and prepare for another round of translation. In eukaryotes this means the 80S ribosome splits into its 40S and 60S subunits. Read more.. What happens during the elongation stage of translation?Sruthi Jagannathan2017-12-19T16:46:46+08:30 What happens during the elongation stage of translation? Elongation occurs over several well-defined steps, beginning with the recognition of the mRNA codons by their corresponding aminoacyl-tRNA. Association with the mRNA occurs via the ribosomal A site and is influenced by various elongation factors. Read more.. How is translation initiated?Sruthi Jagannathan2017-12-19T16:43:25+08:30 How is translation initiated? The first step in translation is known as initiation. Here, the large (60S) and small (40S) ribosomal units are assembled into a fully functional 80S ribosome. This is positioned at the start codon (AUG) of the mRNA strand to be translated. Read more.. What is translation?Sruthi Jagannathan2017-12-19T16:02:08+08:30 What is translation? Translation is a process that involves the synthesis of an amino acid chain from an mRNA blueprint. These polypeptide chains fold into functional proteins. Read more.. What is euchromatin and heterochromatin?Sruthi Jagannathan2017-12-19T15:44:10+08:30 What is euchromatin and heterochromatin? Traditionally, chromatin is classified as either euchromatin or heterochromatin, depending on its level of compaction. Euchromatin has a less compact structure, and is often described as a 11 nm fiber that has the appearance of ‘beads on a string’ where the beads represent nucleosomes and the string represents DNA. In contrast, heterochromatin is more compact, and is often reported as being composed of a nucleosome array condensed into a 30 nm fiber. Read more.. What are transcription factories?Sruthi Jagannathan2017-12-19T15:21:33+08:30 What are transcription factories? Despite 20,000 genes being present in each haploid nucleus, the number of transcription foci is limited to around 2000. These transcription foci, also known as transcriptional factories are distinct submicron nuclear regions that are associated with nascent RNA production and are enriched in RNA polymerase II (RNA pol II) complexes. Read more.. What are telomeres?Sruthi Jagannathan2017-12-19T15:14:11+08:30 What are telomeres? Telomeres are short nucleotide sequences found at the end of linear chromosomes which protect the genetic information. In vertebrates, telomeres have the hexameric sequence TTAGGG. Read more.. What are the various models describing the structural organization of chromosome territories?Sruthi Jagannathan2017-12-19T14:32:09+08:30 What are the various models describing the structural organization of chromosome territories? With the development of high-throughput biochemical techniques, such as 3C (‘chromosome conformation capture’) and 4C (‘chromosome conformation capture-on-chip’ and ‘circular chromosome conformation capture’), numerous spatial interactions between neighbouring chromatin territories have been described. Together, these observations and physical simulations have led to the proposal of various models that aim to define the structural organization of chromosome territories. Read more.. How is transcription regulated in stem cells?Sruthi Jagannathan2017-12-19T13:59:25+08:30 How is transcription regulated in stem cells? Embryonic stem cells are pluripotent in early organism development, but gradually undergo lineage restriction and transform into the stem cells with limited differentiation capacities (e.g., hematopoietic stem cells, neural stem cells). Read more.. How is the nucleus maintained in a prestressed state?Sruthi Jagannathan2017-12-19T12:40:18+08:30 How is the nucleus maintained in a prestressed state? As an integral part of cellular behavior, cells are sensitive to matrix rigidity, local geometry and stress or strain applied by external factors. In recent years, it has been established that an extensive network of protein assembly couples the cytoskeleton to the nucleus and that condensation forces of the chromatin balance cytoskeletal forces resulting in a prestressed nuclear organization. Read more.. What are the stages in DNA replication?Sruthi Jagannathan2017-12-18T16:17:47+08:30 What are the stages in DNA replication? Cells must replicate their DNA before they can divide. This ensures that each daughter cell gets a copy of the genome, and therefore, successful inheritance of genetic traits. DNA replication is an essential process and the basic mechanism is conserved in all organisms. Read more.. How does chromatin remodeling regulate gene transcription?Sruthi Jagannathan2017-12-18T15:53:34+08:30 How does chromatin remodeling regulate gene transcription? While chromosome territory dynamics is believed to regulate gene expression through the redistribution of genes and the subsequent co-localization of these genes with transcription machinery, changes are also commonly made to the chromosome structure at a ‘local’ level. Although these changes do not necessarily involve the redistribution of genes, they do have a significant influence on gene regulation. Read more.. How do chromosome territory dynamics regulate gene expression?Sruthi Jagannathan2017-12-18T15:22:28+08:30 How do chromosome territory dynamics regulate gene expression? The spatial organization of chromatin within the 3-dimensional space of a chromosome territory enables the co-localization of co-transcribed genes and their transcriptional foci. Many gene positioning studies have shown that individual genes often loop out of their chromosomal territory to co-localize with transcription factories. Read more.. What is the chromatin polymer model of chromosome territory organization?steve2018-01-19T15:08:09+08:30 What is the chromatin polymer model of chromosome territory organization? The chromatin polymer models assume a broad range of chromatin loop sizes and predict the observed distances between genomic loci and chromosome territories, as well as the probabilities of contacts being formed between given loci. These models apply physics-based approaches that highlight the importance of entropy for understanding nuclear organization… Read more… What is the Fraser and Bickmore model of chromosome territory organization?steve2018-01-19T15:06:27+08:30 What is the Fraser and Bickmore model of chromosome territory organization? The Fraser and Bickmore model emphasizes the functional importance of giant chromatin loops, which originate from chromosome territories and expand across the nuclear space in order to share transcription factories. In this case, both cis- and trans- loops of decondensed chromatin can be co-expressed and co-regulated by the same transcription factory… Read more… What is the interchromatin network (ICN) model of chromosome territory organization?steve2018-01-19T15:12:33+08:30 What is the interchromatin network (ICN) model of chromosome territory organization? The interchromatin network (ICN) model of chromosome territory organization predicts that intermingling chromatin fibers/loops can make both cis- (within the same chromosome) and trans- (between different chromosomes) contacts. This intermingling is uniform and makes distinction between the chromosome territory and interchromatin compartment functionally meaningless… Read more… What models describe chromosome territories?steve2018-01-19T15:13:49+08:30 What models describe chromosome territories? With the development of high-throughput biochemical techniques, such as 3C (‘chromosome conformation capture’) and 4C (‘chromosome conformation capture-on-chip’ and ‘circular chromosome conformation capture’), numerous spatial interactions between neighbouring chromatin territories have been described. These descriptions have been supplemented with the construction of spatial proximity maps for the entire genome (e.g., for a human lymphoblastoid cell line). Together, these observations and physical simulations have led to the proposal of various models that aim to define the structural organization of chromosome territories… Read more… What are chromosome territories?steve2017-12-19T14:06:59+08:30 What are chromosome territories? During interphase, each chromosome occupies a spatially limited, roughly elliptical domain which is known as a chromosome territory (CT). Each chromosome territory is comprised of higher order chromatin units of ~1 Mb each. These units are likely built up from smaller loop domains. Read more.. What are nucleosomes?steve2017-12-19T14:52:22+08:30 What are nucleosomes? In order to fit DNA into the nucleus, it must be packaged into a highly compacted structure known as chromatin. In the first step of this process DNA is condensed into a 11 nm fiber that represents an approximate 6-fold level of compaction. This is achieved through nucleosome assembly. Read more.. How is DNA packed inside the nucleus?steve2017-12-19T15:34:48+08:30 How is DNA packed inside the nucleus? A series of processes must take place that enable the cell to package DNA within the confines of the nucleus whilst retaining its ability to transcribe and duplicate the entire DNA sequence and maintain its integrity. This is achieved through an elaborate process of DNA condensation that sees DNA packaged into 46 chromosomes (or 23 chromosome pairs) in humans. Read more.. What constitutes the genome?steve2018-01-19T15:32:19+08:30 What constitutes the genome? The human genome contains over 3 billion base pairs or nucleotides. These nucleotides, which are arranged in a linear sequence along DNA (deoxyribonucleic acid), encode every protein and genetic trait in the human body… Read more… How does the cytoskeleton influence nuclear morphology and positioning?steve2018-01-19T16:12:40+08:30 How does the cytoskeleton influence nuclear morphology and positioning? Work by Mazumder et al. ascertained the active involvement of cytoskeletal forces in determining nuclear morphology. Change in nuclear size upon perturbation of actomyosin and microtubules affirmed their roles in exerting tensile and compressive forces respectively on the nucleus, correlating with their functions in the cellular context , … Read more… How does the cytoskeleton couple the plasma membrane to the nucleus?steve2018-01-19T16:24:16+08:30 How does the cytoskeleton couple the plasma membrane to the nucleus? Cytoskeletal filaments bridge the nucleus to the plasma membrane, which in turn is anchored at sub-cellular sites to extracellular substrates via a plethora of proteins that form focal adhesions (FAs). FAs are points of cross-talk between transmembrane integrin receptors and the cytoplasmic filaments and thus are key sites for both biochemical and mechanotransduction pathways… Read more… How is the organization and function of the genome regulated?steve2017-12-18T14:43:41+08:30 How is the organization and function of the genome regulated? Genome regulation encompasses all facets of gene expression, from the biochemical modifications of DNA, to the physical arrangement of chromosomes and the activity of the transcription machinery.The genome regulation programs that cells engage control which proteins are produced, and to what level. The programs are established during stem cell differentiation, and therefore dictate the specialized functions that the cell will carry out throughout its lifetime… Read more… What are intermediate chromatin structures?Andrew Wong2017-12-19T15:02:43+08:30 What are intermediate chromatin structures? Despite the extensive knowledge already gained on the structure of the 11 nm nucleosome fiber, as well as metaphase chromosomes, the intermediate chromatin structures commonly described are largely hypothetical and yet to be observed in vivo.Two popular models that were proposed based on in vitro data are the solenoid and zigzag. Read more.. Close Related Questions
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