Name: dna mismatch repair in replication
Uploaded: 2026-08-26T08:20:56.509Z
Duration: 1 min 48 s
Channel: JoVE

K12 Standards

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New Jersey Student Learning Standards for Science

High School

Life Science

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

From Molecules to Organisms: Structures and Processes

HS-LS1-1

Mismatch Repair

- Na het controleren op fouten in de DNA-replicatie zoals paren van adenine met cytosine kunnen aanhouden.
 En kan worden opgelost via een mechanisme dat mismatch-reparatie wordt genoemd.
 In dit proces worden verkeerd gepaarde bases ge&#xEF;dentificeerd vanwege hun abnormale structuur, door een mismatch-reparatie-eiwit.
Zoals MutS. Andere mismatch-reparatie-eiwitten zoals MutL, identificeer dan de nieuwe streng zodat de streng met de fout wordt hersteld terwijl de sjabloonstreng ongewijzigd blijft.
 Hoe de nieuwe streng wordt ge&#xEF;dentificeerd, hangt af van het organisme.
In E. coli worden specifieke DNA-sequenties gemethaliseerd, waaraan een methylgroep wordt toegevoegd, ergens nadat DNA is gesynthetiseerd.
 E. coli mismatch reparatie-eiwitten detecteren de sequenties die nog niet gemethyleerd zijn, het identificeren van de nieuwe streng.
 In eukaryoten heeft de nieuwe streng meer inkepingen, kleine pauzes dan de sjabloon.
 Eukaryote mismatch-reparatie-eiwitten identificeren de ingesnoerde streng en richt het voor reparatie.
Zodra de nieuwe streng is ge&#xEF;dentificeerd, wordt het gebied met de fout eruitgeknipt door exonuclease enzymen, die nucleotiden verwijderen.
 Uiteindelijk voegt DNA-polymerase de juiste nucleotiden toe en dicht DNA-ligase de gaten aan de randen af, waardoor de fout wordt hersteld.

mismatch-reparatie

<h4>Overzicht</h4>

Organismen zijn in staat om nucleotide-mismatches die optreden tijdens DNA-replicatie te detecteren en te repareren. Dit geavanceerde proces vereist het identificeren van de nieuwe streng en het vervangen van de foutieve basen door correcte nucleotiden. Reparatie van mismatches wordt geco&#xF6;rdineerd door veel eiwitten in zowel prokaryoten als eukaryoten.

<h4>De Mutator Protein-familie speelt een sleutelrol bij het herstel van DNA-mismatches</h4>

Het menselijk genoom bevat meer dan 3 miljard basenparen DNA per cel. Voorafgaand aan de celdeling moet die enorme hoeveelheid genetische informatie worden gerepliceerd. Ondanks het proefleesvermogen van het DNA-polymerase treedt er ongeveer elke 1 miljoen basenparen een kopieerfout op. E&#xE9;n type fout is de mismatch van nucleotiden, bijvoorbeeld de paring van A met G of T met C. Dergelijke mismatches worden gedetecteerd en gerepareerd door de Mutator-eiwitfamilie. Deze eiwitten werden voor het eerst beschreven in de bacterie Escherichia coli (E. coli), maar homologen komen voor in prokaryoten en eukaryoten.

<h4>Mutator S (MutS) initieert het herstel van de mismatch (MMR) door de mismatch te identificeren en eraan te binden. Vervolgens identificeert MutL welke streng de nieuwe kopie is. Alleen de nieuwe streng moet worden gefixeerd, terwijl de sjabloonstreng intact moet blijven. Hoe kan de moleculaire machinerie de nieuw gesynthetiseerde DNA-streng identificeren?</h4>

<h4>Nieuw gesynthetiseerde DNA-strengen verschillen van hun sjabloonstreng</h4>

In veel organismen ontvangen cytosine- en adeninebasen van de nieuwe streng enige tijd na replicatie een methylgroep. Daarom identificeren Mut-eiwitten nieuwe strengen door sequenties te herkennen die nog niet zijn gemethyleerd. Bovendien is de kans groter dat de nieuw gesynthetiseerde streng in eukaryoten kleine breuken vertoont, ook wel DNA-nicks genoemd. De MMR-eiwitten kunnen zo de geknikte streng identificeren en deze ter reparatie richten.

Na identificatie van de nieuwe streng knippen nuclease-enzymen het aangetaste gebied door en snijden de onjuiste nucleotiden weg. Vervolgens vult DNA-polymerase de juiste nucleotiden in en sluit DNA-ligase de suiker-fosfaat-ruggengraat van het DNA af, waardoor het herstelproces van de mismatch wordt voltooid.

<h4>Defecten in het mechanisme voor het herstellen van mismatches kunnen kanker veroorzaken</h4>

De menselijke homoloog van MutS wordt Mutator S-homoloog 2 (MSH2) genoemd. Als de MSH2-functie wordt aangetast, worden puntmutaties en frameshift-mutaties door het hele genoom niet goed gerepareerd. Als gevolg hiervan hebben mensen die een enkel exemplaar van een dergelijk aangetast MSH2-gen bij zich dragen een grotere kans om kanker te ontwikkelen.

<h4>Onherstelde mutaties brandstofaanpassing</h4>

Zou het het beste zijn als MMR nooit een mismatch zou missen? Zelfs lage mutatiesnelheden kunnen een probleem voor een organisme veroorzaken. Mutaties dragen echter ook bij aan genetische variatie in een populatie. Een permissief mismatch-reparatiesysteem in een bacterie kan bijvoorbeeld bij toeval leiden tot de mutatie van een gen dat antibioticaresistentie veroorzaakt, waardoor de kansen op overleving en voortplanting van bacteri&#xEB;n worden vergroot bij blootstelling aan antibiotica. Dit is geweldig nieuws voor de bacteriepopulatie, maar slecht nieuws voor mensen die afhankelijk zijn van antibiotica om infectieziekten te bestrijden.

Sterker nog, de Staphylococcus aureus-stammen worden steeds meer resistent tegen meerdere geneesmiddelen, wat betekent dat weinig of geen antibiotica de verspreiding van deze bacterie bij een pati&#xEB;nt kunnen voorkomen. Infecties met multiresistente bacteri&#xEB;n gaan gepaard met een hoog sterftecijfer bij de mens. Het wijdverbreide gebruik van antibiotica in de veehouderij en de ten onrechte verkorte toediening van antibiotica dragen bij aan de opkomst van multiresistente bacteri&#xEB;n.

Mismatch-reparatie

Overview

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires ...

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Education

JoVE Core

Biology

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DNA Structure and Function

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KEY TERMS AND CONCEPTS

BELANGRIJKE TERMEN EN CONCEPTEN

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 new copy. Only the newly made strand is repaired, while the original template strand stays unchanged.

Cells must also tell the new strand from the old one. In many organisms, cytosine and adenine on the new strand gain a methyl group after replication, so the mismatch repair proteins can recognize DNA that has not yet been methylated. In eukaryotes, the new strand often contains small breaks called DNA nicks, and these nicks also help mark the strand that needs repair.

After the new strand is identified, nuclease enzymes cut out the damaged region. DNA polymerase then fills in the correct nucleotides. DNA ligase seals the sugar-phosphate backbone and completes the repair.

Problems in mismatch repair can lead to disease. The human version of MutS is called MSH2. If MSH2 does not work properly, point mutations and frameshift mutations are not repaired well, and people with one copy of a damaged MSH2 gene have a higher risk of cancer.

Mismatch repair can also affect evolution and antibiotic resistance. If the system is more permissive, a bacterium may gain a mutation that helps it survive antibiotics. This can improve bacterial survival and reproduction, but it is dangerous for people who depend on antibiotics. Staphylococcus aureus is one example, because some strains are becoming multidrug-resistant. These infections are linked to high death rates in humans, and the spread of resistance is worsened by heavy antibiotic use in livestock and by treatment courses that are stopped too early.

DNA Mismatch Repair in Replication

the dna helix

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replication in prokaryotes

How Prokaryotic DNA Is Copied

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replication in eukaryotes

Eukaryotic DNA Copying and Telomeres

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 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...

mismatch repair

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

DNA damage repair by excision protects cells from mutagens that can change DNA. Exposure to environmental mutagens can create bulky lesions that bend the double helix or block transcription. If these changes are not repaired, they can lead to mutations and may contribute to cancer or disease, depending on which DNA sequences are affected. Nucleotide excision repair, or NER, is the process that detects and removes this kind of damage. Specialized proteins scan the DNA for a damaged region, then...

mutations

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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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Protein synthesis begins when ribosomes decode messenger RNA (mRNA) and build a chain of amino acids. This final step of gene expression is called translation. The finished chain is a polypeptide, which can later become a functional protein. Proteins are often called the building blocks of life because they make up much of the body, from muscle fibers to hairs and immune system parts. The instructions for each protein are encoded in genes found in the DNA of every cell. In biology, the central...

bacterial transformation

Griffith’s Mouse Experiment and DNA

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 mismatch repair finds DNA copying errors, fixes the new strand, and why MSH2 defects can raise cancer risk or support antibiotic resistance.

DNA Mismatch Repair in Replication | JoVE K12

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HS-LS1-6

DNA Mismatch Repair in Replication

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