Name: how telomerase protects chromosome ends
Uploaded: 2020-11-23T11:47:35.000Z
Duration: 2 min 41 s
Channel: JoVE

K12 Standards

Alabama Course of Study Science

9-12

Biology

from-molecules-to-organisms-structures-and-processes

From Molecules to Organisms: Structures and Processes

9-12.B.1.3

Telomeres and Telomerase

Le télomère est l'extrémité protectrice d'un chromosome composé de séquences riches en guanine de six nucléotides répétées, par exemple, TTAGGG chez l'homme. Sa longueur varie d'un organisme à l'autre. Dans les chromosomes humains, il y a environ 1 300 à 2 500 répétitions télomères présentes et environ 8 300 chez les souris.Lorsque la machine de réplication de l'ADN atteint les télomères, elle rencontre un problème unique le retrait de la dernière amorce à l'extrémité 5 prime du chromosome entraîne un débordement en 3 prime de l'ADN télémétrique simple brin qui ne peut pas être copié car il n'y a pas d'ADN complémentaire pour servir de modèle pour l'amorce. En raison de ce problème de réplication finale, les télomères peuvent être raccourcis à chaque division cellulaire, ce qui conduit à l'arrêt de la prolifération cellulaire, également connu comme sénescence réplicative. Toutefois, cela peut être évité par la synthèse de nouvelles répétitions de télomère médiées par la télomerase.La télomérase est une enzyme composée à la fois d'ARN avec un modèle pour les répétitions de télomères et de protéines. Elle se lie au débordement en 3 prime des répétitions télomères. Le composant protéique, une transcriptase inverse, étend l'ADN des télomère de six nucléotides à la fois en utilisant l'ARN, une séquence riche en cytosine complémentaire aux répétitions télomères, comme modèle.La télomérase transite ensuite et répète le processus d'addition de nucléotides. L'ADN polymérase alpha, qui contient sa propre sous-unité primase, peut alors ajouter une amorce et copier le brin d'ADN parent étendu. Après l'extension du télomère, le télosome, protéine de six sous-unités, se lie à la pièce double brin du télomère et au débordement en 3 prime qui reste après le retrait de l'amorce.Ce complexe effectue ensuite une boucle et s'insère dans l'ADN en amont, ce qui entraîne une boucle de déplacement, ou boucle D, provoquée par la liaison du débordement en 3 prime à une séquence complémentaire dans la répétition telomère. Cette insertion fixe l'extrémité du télomère en place, formant une boucle de télomère plus grande ou boucle T.La liaison du télosome et la formation de la boucle T protège le chromosome contre la dégradation, la fusion de bout en bout et l'activation inappropriée de la machine de réparation de l'ADN.

<ol>
	<li>Blackburn, Elizabeth H. « Télomères et télomérase : leurs mécanismes d’action et les effets de la modification de leurs fonctions. » Lettres FEBS 579, n° 4 (2005) : 859-862.</li>
	<li>Dahse, Regine, Wolfgang Fiedler et Günther Ernst. « Télomères et télomérase : importance biologique et clinique. » Chimie clinique 43, n° 5 (1997) : 708-714.</li>
	<li>Schmidt, Jens C. et Thomas R. Cech. « Télomérase humaine : biogenèse, trafic, recrutement et activation. » Gènes et développement 29, n° 11 (2015) : 1095-1105.</li>
	<li>De Lange, Titia. « Shelterin : le complexe protéique qui façonne et protège les télomères humains. » Gènes et développement 19, n° 18 (2005) : 2100-2110.</li>
	<li>Sandin, Sara et Daniela Rhodes. « Structure de la télomérase. » Opinion actuelle en biologie structurale 25 (2014) : 104-110.</li>
	<li>Cong, Yu-Sheng, Woodring E. Wright et Jerry W. Shay. « La télomérase humaine et sa régulation. » Microbiol. Mol. Biol. Rev. 66, n° 3 (2002) : 407-425.</li>
</ol>

télomères et télomérase

Dans la réplication de l'ADN eucaryote, un fragment d'ADN simple brin reste à l'extrémité d'un chromosome après le retrait de l'amorce finale. Cette section d’ADN ne peut pas être répliquée de la même manière que le reste du brin car il n’y a pas d’extrémité 3’ à laquelle l’ADN nouvellement synthétisé peut s’attacher. Ce fragment non répliqué entraîne une perte progressive de l'ADN chromosomique lors de chaque duplication cellulaire. De plus, il peut induire une réponse aux dommages à l’ADN par des enzymes qui reconnaissent l’ADN simple brin. Pour éviter cela, une zone tampon composée d'une séquence nucléotidique répétitive et d'un complexe protéique, appelé télomère, est présente aux extrémités des chromosomes et protège les extrémités des chromosomes.

La télomérase, une enzyme ribonucléoprotéique composée à la fois d'ARN et de protéines, peut synthétiser et allonger l'ADN perdu. Le composant ARN de la télomérase (TERC) contient une séquence nucléotidique modèle pour la synthèse des répétitions télomériques. La longueur et la séquence du TERC varient selon les organismes. Chez les ciliés, elle est d'environ 150 nucléotides, alors que chez la levure, elle est d'environ 1 150 nucléotides. Le composant protéique, la télomérase transcriptase inverse (TERT), synthétise de courtes répétitions de télomères en utilisant le brin matrice présent dans le TERC.

Chez les mammifères, le télomère est protégé par la shelterine qui est un complexe de six protéines différentes : le facteur de liaison de la répétition télomérique 1 (TRF1), le facteur de liaison de la répétition télomérique 2 (TRF2), la protection du télomère 1 (POT1), le facteur nucléaire 2 interagissant avec TRF1 (TIN2), la protéine organisatrice TIN2-POT1 (TPP1) et la protéine répresseur/activateur 1 (RAP1).  Les protéines présentes dans le complexe shelterin sont impliquées dans des fonctions importantes telles que le recrutement de la télomérase, la régulation de la longueur des télomères et la fourniture de sites de liaison pour les protéines accessoires.

L'expression de la télomérase peut augmenter la durée de vie d'une cellule et lui permettre de proliférer continuellement, ce qui est une caractéristique des cellules cancéreuses. L'activité de la télomérase a été observée dans près de 90 % des cellules cancéreuses, ce qui en fait une cible des recherches actuelles pour de nouveaux traitements contre le cancer.

Télomères et télomérase

Dans la réplication de l’ADN eucaryote, un fragment d’ADN simple brin reste à l’extrémité d’un chromosome après le retrait de l’amorce finale. Cette section de ...

Education

Enseignement

JoVE Core

Molecular Biology

Biologie moléculaire

Unit 1

Unité 1

DNA Replication

Réplication de l'ADN

KEY TERMS AND CONCEPTS

TERMES ET CONCEPTS CLÉS

how telomerase protects chromosome ends

Telomerase helps protect chromosome ends during eukaryotic DNA replication. When the final primer is removed, a single-stranded DNA fragment can remain at the end of the chromosome. That piece cannot be copied in the same way as the rest of the strand because there is no 3' end for new DNA to attach to.

If this end piece is not replaced, chromosomal DNA is gradually lost each time a cell divides. The exposed single-stranded DNA can also trigger a DNA damage response from enzymes that detect it. To reduce this problem, chromosomes use telomeres, which are protective buffer zones made of repeating nucleotide sequences and a protein complex.

Telomerase is a ribonucleoprotein enzyme, which means it contains both RNA and protein. It can synthesize and extend the DNA that is lost at chromosome ends. The RNA component, called TERC, carries the template sequence used to make telomeric repeats. Its length and sequence differ between organisms. In ciliates, TERC is about 150 nucleotides long, while in yeast it is about 1150 nucleotides long.

The protein part of telomerase is telomerase reverse transcriptase, or TERT. TERT uses the template in TERC to build short telomere repeats. In mammals, telomeres are also protected by shelterin, a complex of six proteins: TRF1, TRF2, POT1, TIN2, TPP1, and RAP1. These proteins help recruit telomerase, control telomere length, and provide binding sites for accessory proteins.

Telomerase can increase how long a cell survives and let it keep dividing. That pattern is a key feature of cancer cells. Telomerase activity is seen in almost 90% of cancer cells, so it is an important target in cancer research and for new treatments.

How Telomerase Protects Chromosome Ends

replication in prokaryotes

Prokaryotic DNA Replication Steps

Prokaryotic DNA replication copies the chromosome before a cell divides. In bacteria, this process starts at a specific DNA site called the origin of replication. From there, the cell builds new DNA strands using enzymes that match each base with its partner. The DNA double helix first opens so replication can begin. As the strands separate, each original strand serves as a template. New nucleotides are added in a set order, which helps the cell make an accurate copy of its genetic material. <br...

replication in eukaryotes

Eukaryotic DNA Replication Steps

Eukaryotic DNA replication copies the genome before a cell divides. In eukaryotes, this process happens in a controlled sequence so each new cell can receive genetic information. Replication begins at specific sites on the DNA called origins. The DNA is opened, and each original strand serves as a template, meaning it guides the building of a new complementary strand. This sets up two DNA molecules from one original molecule. The process then continues as enzymes add matching nucleotides to...

dna base pairing

DNA Base Pair Rules

DNA base pairing follows specific rules that help DNA carry genetic information. In DNA, the bases pair in a regular way, with adenine matching thymine and cytosine matching guanine. These pairs fit together because of their chemical shapes and bonding patterns. These base pairs also support accurate DNA replication. When DNA copies itself, each strand can guide the formation of a new partner strand using the pairing rules. Understanding base pairing helps explain how DNA stays organized and...

the dna replication fork

DNA Replication Stress and Fork Stalling

DNA replication stress and fork stalling can disrupt the copying of a cell’s genome. The replication fork is the Y-shaped site where DNA strands separate and new complementary strands are made at the same time. This linked unwinding and synthesis helps cells duplicate DNA efficiently and with fewer errors. In organisms with small circular DNA, such as E. coli, replication often begins at a single origin. That setup creates two replication forks that move in opposite directions from the opening...

proofreading

Proofreading in DNA Replication

Proofreading in DNA replication helps keep DNA copying accurate. It is a built-in check that reduces mistakes as new DNA is made. DNA polymerase is the enzyme that carries out this checking during replication. When it adds a wrong nucleotide, it can remove the error and replace it with the correct one. This correction step helps maintain the correct DNA sequence. Proofreading is an important part of DNA replication because it supports genetic accuracy. By catching mistakes as they happen, the...

dna helicases

Helicase Motor Proteins in DNA Unwinding

Helicase motor proteins help unwind DNA during key cell processes. They use energy from ATP hydrolysis, which is the breakdown of ATP to release usable energy. This movement lets helicases separate DNA strands when the cell needs access to the genetic code. These enzymes are involved in DNA replication, repair, recombination, and transcription. Helicases are found in all living organisms, but their structure, function, and movement can differ. In prokaryotes, the DnaB helicase moves along the...

the replisome

DNA Replication Teams in the Replisome

DNA replication depends on the replisome, a coordinated complex of proteins that copies DNA with high accuracy. This DNA replication machinery brings many parts together so the leading and lagging strands can be made at the same time. A key idea in this process is the trombone model, proposed by Bruce Alberts in 1980. In this model, a loop forms on the lagging strand when a primer is made. The loop grows as an Okazaki fragment is synthesized, then falls apart when that fragment is finished.

lagging strand synthesis

Okazaki Fragments in DNA Replication

DNA replication uses a leading strand and a lagging strand, and they are made at different rates. The leading strand starts first. The lagging strand starts later, moves more slowly, and is made in pieces. The two strands also differ in direction and starting steps. Leading strand synthesis follows the opening replication fork. Lagging strand synthesis goes in the opposite direction. The leading strand needs one RNA primer, while the lagging strand needs multiple RNA primers. After priming,...

mismatch repair

Fixing DNA Copying Errors

Mismatch repair helps fix DNA copying errors after replication. When DNA is copied, small mistakes can slip through. This repair system finds those mismatches and corrects them before they become permanent changes. The process depends on a group of mutator proteins. These proteins work together to detect the error, remove the incorrect section, and help replace it with the proper DNA sequence. In this way, mismatch repair supports the accuracy of genetic information. If the repair system does...

dna topoisomerases

How Topoisomerases Untwist DNA

DNA topoisomerases are enzymes that untwist DNA when it becomes overcoiled during cell processes such as DNA replication and transcription. They help regulate positive and negative DNA supercoiling without changing the nucleotide sequence. Clockwise overwinding creates positively supercoiled DNA, while counterclockwise underwinding produces negatively supercoiled DNA. Topoisomerases are grouped into two main types. Type I topoisomerases act on one strand of double-stranded DNA, and they...

telomeres and telomerase

Telomerase helps protect chromosome ends during eukaryotic DNA replication. When the final primer is removed, a single-stranded DNA fragment can remain at the end of the chromosome. That piece cannot be copied in the same way as the rest of the strand because there is no 3' end for new DNA to attach to. If this end piece is not replaced, chromosomal DNA is gradually lost each time a cell divides. The exposed single-stranded DNA can also trigger a DNA damage response from enzymes that detect it.

non-nuclear inheritance

Cytoplasmic Inheritance in Cells

Cytoplasmic inheritance explains how some traits are passed through cell structures outside the nucleus. These traits come from organelles such as mitochondria and chloroplasts. They do not follow the usual nuclear pattern of inheritance. Mitochondria and chloroplasts each contain their own DNA. Because of this, they can carry genetic information that affects cell function and certain visible traits. In high school biology, this topic helps explain why not all inherited traits come from...

animal mitochondrial genetics

Animal Mitochondrial DNA and Inheritance

Animal mitochondrial DNA has its own genome, separate from nuclear DNA. It is a double-stranded, closed circular molecule with about 20,000 base pairs. One strand is the heavy, or H-strand, because it is rich in guanine. The other is the light, or L-strand, because it is rich in cytosine. Compared with nuclear DNA, mitochondrial DNA has very little non-coding sequence. It also has no introns. Its genes are packed closely together, and some even overlap. The D-loop is the main non-coding...

comparing mitochondrial, chloroplast, and prokaryotic genomes

comparing-mitochondrial-chloroplast-and-prokaryotic-genomes

How Organelle Genomes Resemble Bacteria

Mitochondrial and chloroplast genomes still keep several traits from their bacterial ancestors. They also show changes that happened after these organelles evolved inside eukaryotic cells. Eukaryotic cells are cells with a nucleus, while prokaryotes are cells without one. Like prokaryotic genomes, mitochondrial and chloroplast genomes do not bind with histone-like proteins. They also do not show the complex chromosome-like packaging seen in eukaryotes. Mitochondria and chloroplasts divide by...

export of mitochondrial and chloroplast genes

export-of-mitochondrial-and-chloroplast-genes

How Organelles Pass Genes to the Nucleus

Eukaryotic cells can carry three genetic systems: nuclear, mitochondrial, and chloroplast. Over time, many genes from mitochondria and chloroplasts have moved into the nucleus. In some plant species, this gene transfer is still happening. This movement has affected large parts of the genome in some organisms. About 18% of the Arabidopsis thaliana nuclear genome is thought to come from the chloroplast's cyanobacterial ancestor. In yeast, around 75% of the genome is derived from the...

single-strand dna binding proteins

How SSB Proteins Protect DNA Strands

Single-strand DNA-binding proteins, or SSB proteins, help protect DNA during replication. When double-stranded DNA is unwound, the two strands separate. SSB proteins bind to the exposed single strands and keep them stable. These proteins bind in a sequence-independent manner. That means the order of the nitrogenous bases does not have to follow a specific pattern for SSB proteins to attach. Their binding straightens single-stranded DNA and makes it more rigid. This support may help DNA...

key terms and concepts

Explore how telomerase, telomeres, and shelterin protect chromosome ends during DNA replication and why telomerase matters in cancer cells.

How Telomerase Protects Chromosome Ends | JoVE K12

molecular biology

JoVE Core Biologie Moléculaire illustre les processus moléculaires au sein de la cellule grâce à des leçons vidéos claires et concises. Les applications de ces concepts sont ensuite démontrées grâce à des expériences concrètes en laboratoire.

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Cell Size

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Eukaryotic Compartmentalization

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The Nucleus

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1. Engage in evidence-based argument to relate a cell's function to the structure, function, and diversity of its components. Examples: Muscle cells have a large number of mitochondria, which create energy for contraction in the form of ATP. Some plant cells have a large vacuole which is used for storage and transport of excess nutrients in changing environments.

9-12.B.1.1

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RNA Structure

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Types of RNA

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Transcription

Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. ...

Bacterial RNA Polymerase

Eukaryotic RNA Polymerases

General Transcription Factors

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RNA Polymerase II Accessory Proteins

Transcription Elongation Factors

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Pre-mRNA Processing: Modification of pre-mRNA Ends

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Pre-mRNA Processing: RNA Splicing

Chromatin Structure and RNA Splicing

Alternative RNA Splicing

Nuclear Export of mRNA

Transfer RNA Synthesis

Ribosomal RNA Synthesis

The Nucleolus

Additional Subnuclear Structures

Translation

Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes ...

tRNA Activation

Initiation of Translation

Termination of Translation

Improving Translational Accuracy

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Prokaryotic Transcriptional Activators and Repressors

Nonsense-mediated mRNA Decay

The Eukaryotic Promoter Region

Molecular Chaperones and Protein Folding

Co-activators and Co-repressors

The Proteasome

Master Transcription Regulators

Regulated Protein Degradation

Regulated mRNA Transport

Proteins: From Genes to Degradation

mRNA Stability and Gene Expression

Cell Specific Gene Expression

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between ...

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Regulation of Expression Occurs at Multiple Steps

Small interfering RNAs (siRNA)

Cis-regulatory Sequences

lncRNA - Long Non-coding RNAs

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Cooperative Binding of Transcription Regulators

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. ...

2. Obtain and evaluate information to explain the role of DNA and RNA in transcription and translation leading to protein synthesis and cellular function.

9-12.B.1.2

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Genomic DNA in Eukaryotes

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a. Use a model to describe the structure and sequence of DNA, including nucleotide structure, base pairing, and the structure of the helix.

9-12.B.1.2.a

How Telomerase Protects Chromosome Ends

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