Telomere in the context of "Cellular senescence"

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⭐ Core Definition: Telomere

A telomere (/ˈtɛləmɪər, ˈtlə-/; from Ancient Greek τέλος (télos) 'end' and μέρος (méros) 'part') is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most or even all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.

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👉 Telomere in the context of Cellular senescence

Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process called the Hayflick limit is also known as "replicative senescence", since it is brought about through replication. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress-inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things.

The physiological importance of cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. Senescent cells contribute to the aging phenotype, including frailty syndrome, sarcopenia, and aging-associated diseases. Senescent astrocytes and microglia contribute to neurodegeneration.

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In this Dossier

Telomere in the context of Barbara McClintock

Barbara McClintock (June 16, 1902 – September 2, 1992) was an American scientist and cytogeneticist who was awarded the 1983 Nobel Prize in Physiology or Medicine. McClintock received her PhD in botany from Cornell University in 1927. There she started her career as the leader of the development of maize cytogenetics, the focus of her research for the rest of her life. From the late 1920s, McClintock studied chromosomes and how they change during reproduction in maize. She developed the technique for visualizing maize chromosomes and used microscopic analysis to demonstrate many fundamental genetic ideas. One of those ideas was the notion of genetic recombination by crossing-over during meiosis—a mechanism by which chromosomes exchange information. She is often erroneously credited with producing the first genetic map for maize, linking regions of the chromosome to physical traits. She demonstrated the role of the telomere and centromere, regions of the chromosome that are important in the conservation of genetic information. She was recognized as among the best in the field, awarded prestigious fellowships, and elected a member of the National Academy of Sciences in 1944.

During the 1940s and 1950s, McClintock discovered transposons and used it to demonstrate that genes are responsible for turning physical characteristics on and off. She developed theories to explain the suppression and expression of genetic information from one generation of maize plants to the next. Due to skepticism of her research and its implications, she stopped publishing her data in 1953.

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Telomere in the context of SnRNA

Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcribed by either RNA polymerase II or RNA polymerase III. Their primary function is in the processing of pre-messenger RNA (hnRNA) in the nucleus. They have also been shown to aid in the regulation of transcription factors (7SK RNA) or RNA polymerase II (B2 RNA), and in the maintenance of telomeres.

snRNA are always associated with a set of specific proteins, and the complexes are referred to as small nuclear ribonucleoproteins (snRNP, often pronounced "snurps"). Each snRNP particle is composed of an snRNA component and several snRNP-specific proteins (including Sm proteins, a family of nuclear proteins). The most common human snRNA components of these complexes are known, respectively, as: U1 spliceosomal RNA, U2 spliceosomal RNA, U4 spliceosomal RNA, U5 spliceosomal RNA, and U6 spliceosomal RNA. Their nomenclature derives from their high uridine content.

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Telomere in the context of Telomerase

Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.

Telomerase is a reverse transcriptase enzyme that carries its own RNA molecule (e.g., with the sequence 3′-CCCAAUCCC-5′ in Trypanosoma brucei) which is used as a template when it elongates telomeres. Telomerase is active in gametes and most cancer cells, but is normally absent in most somatic cells.

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Telomere in the context of Non-coding DNA

Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regulatory RNAs). Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional, such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses. Regions that are completely nonfunctional are called junk DNA.

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Telomere in the context of Human genome

The human genome is a complete set of DNA sequences for each of the 22 autosomes and the two distinct sex chromosomes (X and Y). A small DNA molecule is found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome.

Human genomes include both genes and various other types of functional DNA elements. The latter is a diverse category that includes regulatory DNA scaffolding regions, telomeres, centromeres, and origins of replication. In addition, there are large numbers of transposable elements, inserted viral DNA, non-functional pseudogenes and simple, highly repetitive sequences. Introns make up a large percentage of the human genome.

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Telomere in the context of Circular chromosome

A circular chromosome is a chromosome in bacteria, archaea, mitochondria, and chloroplasts, in the form of a molecule of circular DNA, unlike the linear chromosome of most eukaryotes.

Most prokaryote chromosomes contain a circular DNA molecule. This has the major advantage of having no free ends (telomeres) to the DNA. By contrast, most eukaryotes have linear DNA requiring elaborate mechanisms to maintain the stability of the telomeres and replicate the DNA. However, a circular chromosome has the disadvantage that after replication, the two progeny circular chromosomes can remain interlinked or tangled, and they must be extricated so that each cell inherits one complete copy of the chromosome during cell division.

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Telomere in the context of Non-homologous end joining

Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. It is called "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair (HDR), which requires a homologous sequence to guide repair. NHEJ is active in both non-dividing and proliferating cells, while HDR is not readily accessible in non-dividing cells. The term "non-homologous end joining" was coined in 1996 by Moore and Haber.

NHEJ is typically guided by short homologous DNA sequences called microhomologies. These microhomologies are often present in single-stranded overhangs on the ends of double-strand breaks. When the overhangs are perfectly compatible, NHEJ usually repairs the break accurately. Imprecise repair leading to loss of nucleotides can also occur, but is much more common when the overhangs are not compatible. Inappropriate NHEJ can lead to translocations and telomere fusion, hallmarks of tumor cells.

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Telomere in the context of Gerontogens

Gerontogens are environmental agents that can accelerate aging in some animals, including humans. Gerontogens are typically toxic chemical agents, such as those found in cigarette smoke. However, many other things can act as gerontogens, including ultraviolet radiation, chemotherapy treatment, and arsenic.

Gerontogens work in two different ways. They can shorten telomeres, repetitive nucleotide sequences at the end of chromosomes, which accelerates cell destruction. Gerontogens can also accelerate the rate of cellular senescence, where normal diploid cells cease to divide. This can be measured using the body's levels of the protein p16.

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