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

The telomere is the protective end of a chromosome, composed of repeating six nucleotide guanine-rich sequences, for example, TTAGGG in humans.&#160;
Its length varies from organism to organism. In human chromosomes, there are approximately 1300 to 2500 telomere repeats present and around 8300 in mice.
When the DNA replication machinery reaches the telomeres, it encounters a unique problem: the removal of the last primer at the 5&#8217; end of the chromosome results in a 3&#8217; overhang of single stranded telomeric DNA that cannot be copied because there is no complementary DNA to act as a template for the primer.&#160;
Due to this end-replication problem, the telomeres can become shortened with each cell division which eventually leads to the arrest of cell proliferation, also known as replicative senescence; however, this can be prevented by telomerase mediated synthesis of new telomere repeats.&#160;&#160;
Telomerase is an enzyme composed of both RNA with a template for telomere repeats and protein. It binds to the 3&#8217; overhang of the telomere repeats.
The protein component, a reverse transcriptase, extends the telomere DNA six nucleotides at a time, using the RNA, a cytosine-rich sequence complementary to the telomere repeats, as a template.
Telomerase then translocates and repeats the process of the addition of nucleotides.
DNA polymerase &#945;, which contains its own primase subunit, can then add a primer and copy the extended parent DNA strand.
After telomere extension, shelterin, a six-subunit protein, binds to the double-stranded piece of the telomere and the 3 prime overhang that remains after the removal of the primer.
This complex then loops back and inserts itself in the upstream DNA resulting in a displacement loop, or D-loop, caused by the 3&#8217; overhang binding to a complementary sequence in the telomere repeat. This insertion anchors the end of the telomere in place, forming a larger telomere loop, or T-loop.
The binding of shelterin and the formation of the T-loop protects the chromosome from degradation, end-to-end fusion, and inappropriate activation of the DNA repair machinery.

telomeren en telomerase

Bij eukaryotische DNA-replicatie blijft er een enkelstrengig DNA-fragment achter aan het uiteinde van een chromosoom na verwijdering van de laatste primer. Dit stukje DNA kan niet op dezelfde manier worden gerepliceerd als de rest van de streng, omdat er geen 3’-uiteinde is waaraan het nieuw gesynthetiseerde DNA zich kan hechten. Dit niet-gerepliceerde fragment resulteert in geleidelijk verlies van het chromosomale DNA tijdens elke celduplicatie. Bovendien kan het een reactie op DNA-schade veroorzaken door enzymen die enkelstrengs DNA herkennen. Om dit te voorkomen, is aan de uiteinden van de chromosomen een bufferzone aanwezig die bestaat uit een zich herhalende nucleotidesequentie en een eiwitcomplex, een telomeer genaamd, die de uiteinden van de chromosomen beschermt.

Telomerase, een ribonucleoproteïne-enzym dat bestaat uit zowel RNA als eiwitten, kan het verloren DNA synthetiseren en verlengen. Telomerase RNA-component (TERC) bevat een template-nucleotidesequentie voor de synthese van de telomere herhalingen. De lengte en sequentie van de TERC variëren tussen organismen. In ciliaten is deze ongeveer 150 nucleotiden lang, terwijl deze in gist ongeveer 1150 nucleotiden bedraagt. De eiwitcomponent, telomerase reverse transcriptase (TERT), synthetiseert korte telomeerherhalingen met behulp van de matrijsstreng die aanwezig is in de TERC.

Bij zoogdieren wordt de telomeer beschermd door Shelterin, een complex van zes verschillende eiwitten: telomere herhalingsbindende factor 1 (TRF1), telomere herhalingsbindende factor 2 (TRF2), bescherming van telomere 1 (POT1), TRF1-interagerende nucleaire factor 2 ( TIN2), TIN2-POT1 organiserend eiwit (TPP1) en repressor/activatoreiwit 1 (RAP1). Eiwitten die aanwezig zijn in het shelterin-complex zijn betrokken bij belangrijke functies zoals de rekrutering van telomerase, regulering van de lengte van telomeren en het verschaffen van bindingsplaatsen voor aanvullende eiwitten.

Telomerase-expressie kan de levensduur van een cel verlengen en ervoor zorgen dat deze zich continu kan vermenigvuldigen, een kenmerkend kenmerk van een kankercel. Telomerase-activiteit is waargenomen in bijna 90% van de kankercellen, waardoor ze een doelwit zijn van huidig onderzoek naar nieuwe kankerbehandelingen.

Telomeren en telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of ...

Education

JoVE Core

Molecular Biology

Moleculaire biologie

Unit 1

DNA Replication

DNA-replicatie

KEY TERMS AND CONCEPTS

BELANGRIJKE TERMEN EN CONCEPTEN

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

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9-12.B.1.2.a

How Telomerase Protects Chromosome Ends

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