Name: dna polymerase fixes replication errors
Uploaded: 2026-06-01T06:28:10.056Z
Duration: 1 min 43 s
Channel: JoVE

K12 Standards

Virginia  Standards of Learning

HIgh School

Life Science

LS.10

LS.10.a

Proofreading

During DNA replication, free nucleotides in the cell are added to the new strand in a sequence complementary to the template. Adenine pairs with thymine, and cytosine pairs with guanine.
 
 Sometimes, nucleotides pair incorrectly, such as when adenine pairs with cytosine. DNA polymerase proofreading helps fix these errors and reduces the chance of mutations. If they are not corrected, these errors can cause disease.
 
 First, DNA polymerase binds more strongly to correctly paired nucleotides. This reduces the chance of incorrect pairings.
 
 Second, as nucleotides begin pairing with the template, DNA polymerase undergoes a conformational change. This change causes incorrectly paired nucleotides to detach, allowing the correct nucleotides to be added.
 
 Third, if an incorrect nucleotide is added to the three-prime end of the growing DNA chain, the mismatch distorts the DNA structure and pauses DNA polymerase movement.
 
 DNA polymerase has three-prime-to-five-prime exonuclease activity, which lets it remove an incorrectly added nucleotide. It then inserts the correct nucleotide. This process is called exonucleolytic proofreading.
 
 These steps help keep DNA replication accurate by separating nucleotide selection from error correction.

Barbari, Stephanie R. et Polina V. Shcherbakova. « Défauts de l’ADN polymérase répliquative dans les cancers humains : conséquences, mécanismes et implications pour la thérapie. » Réparation de l’ADN 56 (2017) : 16-25. [<a href="https://doi.org/10.1016/j.dnarep.2017.06.003">Source</a>]

relecture

<h4>Aper&#xE7;u</h4>
 
 La synth&#xE8;se de nouvelles mol&#xE9;cules d&#x2019;ADN commence lorsque la polym&#xE9;rase d&#x2019;ADN relie les nucl&#xE9;otides dans une s&#xE9;quence compl&#xE9;mentaire au brin d&#x2019;ADN matrice. L&#x2019;ADN polym&#xE9;rase a plus d&#x2019;affinit&#xE9; pour la base correcte afin d&#x2019;assurer la fid&#xE9;lit&#xE9; lors de la r&#xE9;plication de l&#x2019;ADN. L&#x2019;ADN polym&#xE9;rase fait en outre la relecture pendant la r&#xE9;plication, &#xE0; l&#x2019;aide d&#x2019;un domaine d&#x2019;exonucl&#xE9;ase qui coupe les nucl&#xE9;otides incorrects du brin d&#x2019;ADN naissant.
 
 <h4>Les erreurs pendant la r&#xE9;plication sont corrig&#xE9;es par l&#x2019;enzyme d&#x2019;ADN polym&#xE9;rase</h4>
 
 L&#x2019;ADN g&#xE9;nomique est synth&#xE9;tis&#xE9; dans le sens de 5&#x2019; &#xE0; 3&#x2019;. Chaque cellule contient un certain nombre de polym&#xE9;rases d&#x2019;ADN qui jouent des r&#xF4;les diff&#xE9;rents dans la synth&#xE8;se et la correction des erreurs dans l&#x2019;ADN ; l&#x2019;ADN polym&#xE9;rase delta et epsilon poss&#xE8;dent la facult&#xE9; de relecture au moment de la r&#xE9;plication de l&#x2019;ADN nucl&#xE9;aire. Ces polym&#xE9;rases &#x201C; lisent &#x201D; chaque base apr&#xE8;s qu&#x2019;elle soit ajout&#xE9;e au nouveau brin. Si la base nouvellement ajout&#xE9;e est incorrecte, la polym&#xE9;rase inverse la direction (passant de 3&#x2019; &#xE0; 5&#x2019;)&#xA0;et utilise un domaine exonucl&#xE9;olytique pour couper la base incorrecte. Par la suite, elle est remplac&#xE9;e par la base correcte.
 
 <h4>Les mutations dans le domaine de l&#x2019;exonucl&#xE9;ase de l&#x2019;ADN polym&#xE9;rase sont li&#xE9;es aux cancers</h4>
 
 La relecture est importante pour emp&#xEA;cher que des mutations se produisent dans l&#x2019;ADN nouvellement synth&#xE9;tis&#xE9;, mais que se passe-t-il lorsque le m&#xE9;canisme de relecture &#xE9;choue ? Lorsqu&#x2019;une mutation modifie le domaine de l&#x2019;exonucl&#xE9;ase de l&#x2019;ADN polym&#xE9;rase, elle perd la facult&#xE9; d&#x2019;&#xE9;liminer les nucl&#xE9;otides incorrects. En cons&#xE9;quence, les mutations peuvent s&#x2019;accumuler rapidement dans tout le g&#xE9;nome. Ce type de mutation a &#xE9;t&#xE9; li&#xE9; &#xE0; divers types de cancer.
 
 <h4>La polym&#xE9;rase d&#x2019;ADN de faible fid&#xE9;lit&#xE9; peut g&#xE9;n&#xE9;rer des s&#xE9;quences d&#x2019;ADN mut&#xE9;es</h4>
 
 Des ADN polym&#xE9;rases modifi&#xE9;es sont utilis&#xE9;es en science de laboratoire pour la r&#xE9;action en cha&#xEE;ne par polym&#xE9;rase (PCR), une technique in vitro pour fabriquer de nombreuses copies de fragments sp&#xE9;cifiques d&#x2019;ADN. Alors que les polym&#xE9;rases de haute fid&#xE9;lit&#xE9; sont utilis&#xE9;es lorsqu&#x2019;il est important que le produit final soit parfait, certaines techniques, telles que la PCR sujettes aux erreurs, cherchent &#xE0; g&#xE9;n&#xE9;rer des mutations dans une portion d&#x2019;ADN expr&#xE8;s. Ces techniques utilisent des polym&#xE9;rases qui ont une facult&#xE9; de relecture affaiblie.

Relecture

Overview

Synthesis of new DNA molecules starts when DNA polymerase links nucleotides together in a sequence that is complementary to the template DNA ...

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DNA Structure and Function

Structure et fonction de l'ADN

KEY TERMS AND CONCEPTS

TERMES ET CONCEPTS CLÉS

dna polymerase fixes replication errors

DNA polymerase helps copy DNA and fix mistakes during replication. It adds nucleotides in a sequence that matches the template DNA strand. The enzyme also has a higher affinity for the correct base, which helps keep DNA replication accurate.

As new genomic DNA is made, it is synthesized in the 5’ to 3’ direction. In many cells, DNA polymerases have different jobs in this process. DNA polymerase delta and DNA polymerase epsilon can proofread when nuclear DNA is being copied.

These polymerases check each base after it is added to the new strand. If the new base is wrong, the enzyme moves backward from 3’ to 5’. It then uses an exonuclease domain, a section that cuts DNA, to remove the incorrect nucleotide. The correct base is then added in its place.

Proofreading helps prevent mutations in newly made DNA. If a mutation changes the exonuclease domain, the polymerase can no longer remove wrong nucleotides well. Errors can build up quickly across the genome, and this kind of defect has been linked to cancer.

Modified DNA polymerases are also useful in the lab during polymerase chain reaction, or PCR. PCR is an in vitro method for making many copies of specific DNA fragments. High-fidelity polymerases are used when the final DNA should be accurate, while error-prone PCR uses low-fidelity polymerases with reduced proofreading to create mutations on purpose.

DNA Polymerase Fixes Replication Errors

the dna helix

How DNA Stores Genetic Information

DNA stores genetic information that is passed from one generation to the next in organisms and most viruses. It is built from two strands of nucleotides that twist together into a double helix. The story of how scientists uncovered this structure developed step by step over nearly a century. Each DNA strand is made of nucleotides. A nucleotide contains the sugar deoxyribose, a phosphate group, and one of four nitrogen bases: adenine (A), guanine (G), cytosine (C), or thymine (T). Adenine and...

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Eukaryotic DNA copying is tightly regulated and must duplicate many linear chromosomes before cell division. The process is highly conserved and uses many proteins with specialized roles. It moves through initiation, elongation, and termination, and it ends with two complete sets of chromosomes in the nucleus. Eukaryotic replication shares basic steps with prokaryotic DNA replication, but the larger genome and linear chromosomes require more proteins. Replication begins at multiple origins of...

proofreading

DNA polymerase helps copy DNA and fix mistakes during replication. It adds nucleotides in a sequence that matches the template DNA strand. The enzyme also has a higher affinity for the correct base, which helps keep DNA replication accurate. As new genomic DNA is made, it is synthesized in the 5’ to 3’ direction. In many cells, DNA polymerases have different jobs in this process. DNA polymerase delta and DNA polymerase epsilon can proofread when nuclear DNA is being copied. These polymerases...

mismatch repair

DNA Mismatch Repair in Replication

DNA mismatch repair fixes copying errors that happen during DNA replication. When DNA polymerase makes a mistake, the cell can detect a wrong base pair, such as A with G or T with C, and replace it with the correct nucleotide. This repair system works in both prokaryotes and eukaryotes and depends on several proteins. The Mutator protein family plays a central role in this process. In bacteria such as Escherichia coli, MutS first binds the mismatch. MutL then helps identify which strand is the...

nucleotide excision repair

DNA Damage Repair by Excision

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mutations

DNA Changes From Point Mutations to UV Damage

Mutations are changes in the DNA sequence. They can happen by chance during DNA copying, or they can be caused by environmental factors such as radiation and chemicals. Scientists also describe mutations by how much DNA they affect, how they change a protein, and whether they happen in body cells or germline cells. Some mutations affect only one nucleotide, which is a point mutation. When a point mutation falls inside a gene, the outcome depends on how the amino acid sequence changes. A silent...

transcription

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translation

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bacterial transformation

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Bacterial transformation explains how DNA can move into bacteria and change their traits. Frederick Griffith first noticed this in 1928 while studying pneumonia-causing Streptococcus pneumoniae in mice. He compared one pathogenic strain with one non-pathogenic strain and found that only the pathogenic strain killed the host mice. Griffith made an unexpected discovery when he killed the pathogenic bacteria and mixed their remains with live, non-pathogenic bacteria. The mixture killed the mice,...

key terms and concepts

Learn how DNA polymerase proofreads new DNA, removes mismatched bases with exonuclease activity, and how low-fidelity enzymes are used in PCR.

DNA Polymerase Fixes Replication Errors | JoVE K12

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

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BIO.6.A

new-york-state-science-learning-standards

New York State Science Learning Standards

Inheritance and Variation of Traits

HS-LS3-1.

The DNA Helix

Overview

Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most ...

DNA Packaging

Overview

Eukaryotes have large genomes compared to prokaryotes. In order to fit their genomes into a cell, eukaryotes must pack their DNA tightly inside ...

Organization of Genes

Overview

The genomes of eukaryotes can be structured in several functional categories. A strand of DNA is comprised of genes and intergenic regions. ...

Replication in Prokaryotes

Overview

DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to ...

Replication in Eukaryotes

Overview

In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high ...

Synthesis of new DNA molecules starts when DNA polymerase links nucleotides together in a sequence that is complementary to the template DNA strand. DNA ...

Mutations

Overview

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. ...

Transcription

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

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following ...

Bacterial Transformation

In 1928, bacteriologist Frederick Griffith worked on a vaccine for pneumonia, which is caused by Streptococcus pneumoniae bacteria. Griffith studied two ...

What is Gene Expression?

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Gene expression is the process in which DNA&nbsp;directs the synthesis of functional products, that is, proteins. Cells can regulate gene ...

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The central dogma of biology states that information encoded in the DNA is transferred to messenger RNA (mRNA), which then directs the synthesis ...

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of ...

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The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form ...

RNA Stability

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Types of RNA

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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs ...

MicroRNAs

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RNA Splicing

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Epigenetic Regulation

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Operons

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Proteins: From Genes to Degradation

The student will investigate and understand that organisms reproduce and transmit genetic information to new generations. Key ideas include DNA has a role in making proteins that determine organism traits;

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Meiosis is the process by which diploid cells divide to produce haploid daughter cells. In humans, each diploid cell contains 46 chromosomes, half from ...

Meiosis I

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Meiosis II

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Crossing Over

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Nondisjunction

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LS.10.b

Genetic Lingo

Overview

An organism is diploid if it inherits two variants, or alleles, of each gene, one from each parent. These two alleles constitute the genotype ...

Punnett Squares

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Monohybrid Crosses

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In the 1850s and 1860s, Gregor Mendel investigated inheritance by performing monohybrid crosses in pea plants. He crossed two plants that were ...

Dihybrid Crosses

Overview

To determine whether traits are inherited together or separately, Gregor Mendel crossed pea plants that differed in two traits. These parental ...

Law of Segregation

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Law of Independent Assortment

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Test Cross

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An allele is ...

Pedigree Analysis

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X-linked Traits

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The student will investigate and understand that organisms reproduce and transmit genetic information to new generations. Key ideas include Punnett squares are mathematical models used to predict the probability of traits in offspring.

LS.10.c

DNA Polymerase Fixes Replication Errors

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