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

K12 Standards

new-jersey-student-learning-standards-for-science

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

Ap&#xF3;s a revis&#xE3;o, erros na replica&#xE7;&#xE3;o do DNA como emparelhamento da adenina com a citosina podem persistir. E podem ser corrigidos por meio de um mecanismo denominado reparo de incompatibilidade. Neste processo bases mal reparadas s&#xE3;o identificadas devido a sua estrutura anormal, por uma prote&#xED;na de reparo de incompatibilidade.Como a MutS. Outras prote&#xED;nas de reparo de incompatibilidade como a MutL, em seguida, identificam a nova vertente de modo que a vertente com o erro seja reparada enquanto a vertente modelo permanece inalterada. Como a nova vertente &#xE9; identificada depende do organismo.Em E.coli, as sequ&#xEA;ncias de DNA espec&#xED;ficas s&#xE3;o metiladas, tem um grupo metil adicionado, algum tempo depois de o DNA ter sido sintetizado. As prote&#xED;nas de repara&#xE7;&#xE3;o de incompatibilidade da E.coli detetam as sequ&#xEA;ncias que ainda n&#xE3;o foram metiladas, identificando a nova vertente. Em eucariontes, a novo vertente &#xE9; mais prov&#xE1;vel para ter entalhes, quebras pequenas, do que o molde.As prote&#xED;nas de reparo de incompatibilidade eucari&#xF3;ticas identificam o fio cortado e o direcionam para reparo. Uma vez que a nova vertente &#xE9; identificada, a regi&#xE3;o com o erro &#xE9; cortada por enzimas exonuclease, que removem os nucleot&#xED;deos. Finalmente a DNA polimerase adiciona os nucleot&#xED;deos corretos e a DNA ligase sela as lacunas nas bordas reparando o erro.

"Mecanismos e funções do reparo de incompatibilidade de DNA." Cell Research 18, nº 1: 85–98. [<a href="https://doi.org/10.1038/cr.2007.115">Fonte</a>]

Centros de Controle e Prevenção de Doenças. "As maiores ameaças resistentes a antibióticos nos EUA" CDC.gov. [<a href="https://www.cdc.gov/drugresistance/biggest_threats.html">Fonte</a>]

reparação de pares errados

<h4>Vis&#xE3;o Geral</h4>
 
 Os organismos s&#xE3;o capazes de detectar e corrigir incompatibilidades de nucle&#xF3;tidos que ocorrem durante a replica&#xE7;&#xE3;o do DNA. Este processo sofisticado requer a identifica&#xE7;&#xE3;o da nova cadeia e substitui&#xE7;&#xE3;o das bases erradas por nucle&#xF3;tidos corretos. A repara&#xE7;&#xE3;o de pares errados &#xE9; coordenada por muitas prote&#xED;nas tanto em procariotas como em eucariotas.
 
 <h4>A Fam&#xED;lia de Prote&#xED;nas Mutator Desempenha um Papel Fundamental na Repara&#xE7;&#xE3;o de Pares Errados no DNA</h4>
 
 O genoma humano tem mais de 3 mil milh&#xF5;es de pares de bases de DNA por c&#xE9;lula. Antes da divis&#xE3;o celular, essa grande quantidade de informa&#xE7;&#xE3;o gen&#xE9;tica precisa ser replicada. Apesar da capacidade de revis&#xE3;o da DNA polimerase, um erro de c&#xF3;pia ocorre aproximadamente a cada 1 milh&#xE3;o de pares de bases. Um tipo de erro &#xE9; a incompatibilidade de nucle&#xF3;tidos, por exemplo, o emparelhamento de A com G ou T com C. Tais incompatibilidades s&#xE3;o detectadas e reparadas pela fam&#xED;lia de prote&#xED;nas Mutator. Essas prote&#xED;nas foram descritas pela primeira vez na bact&#xE9;ria Escherichia coli (E. coli), mas existem hom&#xF3;logos em procariotas e eucariotas.
 
 A Mutator S (MutS) inicia a repara&#xE7;&#xE3;o de pares errados (MMR) identificando e ligando-se ao local de incompatibilidade. Posteriormente, a MutL identifica qual das cadeias &#xE9; a nova c&#xF3;pia. Apenas a nova cadeia necessita ser reparada enquanto que a cadeia molde precisa permanecer intacta. Como pode a maquinaria molecular identificar a cadeia de DNA rec&#xE9;m-sintetizada?
 
 <h4>Cadeias de DNA Rec&#xE9;m-Sintetizadas Diferem da sua Cadeia Molde</h4>
 
 Em muitos organismos, as bases de citosina e adenina da nova cadeia recebem um grupo metilo algum tempo ap&#xF3;s a replica&#xE7;&#xE3;o. Portanto, as prote&#xED;nas Mut identificam novas cadeias reconhecendo sequ&#xEA;ncias que ainda n&#xE3;o foram metiladas. Al&#xE9;m disso, &#xE9; mais prov&#xE1;vel que a cadeia rec&#xE9;m-sintetizada em eucariotas tenha pequenas quebras, tamb&#xE9;m chamadas de cortes de DNA. As prote&#xED;nas MMR podem, assim, identificar a cadeia recortada e direcion&#xE1;-la para repara&#xE7;&#xE3;o.
 
 Ap&#xF3;s a identifica&#xE7;&#xE3;o da nova cadeia, enzimas nuclease cortam a regi&#xE3;o afetada e removem os nucle&#xF3;tidos incorretos. Em seguida, a DNA polimerase preenche os nucle&#xF3;tidos corretos e a DNA ligase sela o esqueleto de a&#xE7;&#xFA;car-fosfato do DNA, finalizando assim o processo de repara&#xE7;&#xE3;o de pares errados.
 
 <h4>Defeitos no Mecanismo de Repara&#xE7;&#xE3;o de Pares Errados Podem Causar Cancro</h4>
 
 O hom&#xF3;logo humano da MutS &#xE9; chamado de Mutator S hom&#xF3;logo 2 (MSH2). Se a fun&#xE7;&#xE3;o da MSH2 estiver comprometida, muta&#xE7;&#xF5;es pontuais e muta&#xE7;&#xF5;es por mudan&#xE7;a de matriz por todo o genoma n&#xE3;o s&#xE3;o adequadamente reparadas. Como consequ&#xEA;ncia, os seres humanos que carreguem uma &#xFA;nica c&#xF3;pia de um MSH2 t&#xE3;o comprometido t&#xEA;m maior probabilidade de desenvolver cancro.
 
 <h4>Muta&#xE7;&#xF5;es N&#xE3;o Reparadas Alimentam Adapta&#xE7;&#xE3;o</h4>
 
 Seria melhor se a MMR nunca perdesse uma incompatibilidade? Mesmo baixas taxas de muta&#xE7;&#xE3;o podem causar um problema para um organismo. No entanto, muta&#xE7;&#xF5;es tamb&#xE9;m contribuem para a varia&#xE7;&#xE3;o gen&#xE9;tica em uma popula&#xE7;&#xE3;o. Por exemplo, um sistema de repara&#xE7;&#xE3;o permissivo em uma bact&#xE9;ria pode, por acaso, levar &#xE0; muta&#xE7;&#xE3;o de um gene que confere resist&#xEA;ncia a antibi&#xF3;ticos, aumentando assim a probabilidade de sobreviv&#xEA;ncia e reprodu&#xE7;&#xE3;o bacteriana quando exposta a antibi&#xF3;ticos. Esta &#xE9; uma &#xF3;ptima not&#xED;cia para a popula&#xE7;&#xE3;o bacteriana, mas m&#xE1;s not&#xED;cias para os seres humanos que dependem de antibi&#xF3;ticos para combater doen&#xE7;as infecciosas.
 
 De fato, as estirpes de Staphylococcus aureus ganham cada vez mais resist&#xEA;ncia a m&#xFA;ltiplos f&#xE1;rmacos, o que significa que poucos ou nenhum antibi&#xF3;tico pode impedir a propaga&#xE7;&#xE3;o desta bact&#xE9;ria em um paciente. Infec&#xE7;&#xF5;es com bact&#xE9;rias multirresistentes est&#xE3;o associadas a uma alta taxa de mortalidade em humanos. O uso generalizado de antibi&#xF3;ticos na produ&#xE7;&#xE3;o pecu&#xE1;ria e a administra&#xE7;&#xE3;o inadequadamente curta de antibi&#xF3;ticos contribuem para o aparecimento de bact&#xE9;rias multirresistentes.

Reparação de Pares Errados

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

Biologia

Genetics

Genética

DNA Structure and Function

Estrutura e Função do DNA

KEY TERMS AND CONCEPTS

TERMOS-CHAVE E CONCEITOS

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

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...

dna packaging

Chromatin and Histones in DNA Packing

Eukaryotic cells must pack long DNA molecules into the nucleus, and chromatin makes that possible. DNA wraps around proteins called histones to form nucleosomes, which are the main unit of DNA packaging. Nucleosomes then coil into compact chromatin fibers. The amount of DNA in a cell is much larger than it first seems. A single human skin cell has about 3 billion base pairs of DNA, and if that DNA were stretched out in a line, it would be about 2 meters long. With about 50 trillion cells in...

organization of genes

Genes, Introns, and Regulatory DNA

Eukaryotic genes are arranged within DNA along with non-coding regions that help control gene activity. A DNA strand includes genes and intergenic regions, which are the stretches between genes. These regions do not code for proteins, but they can contain important regulatory elements such as promoters, enhancers, and silencers. A gene itself is not a single continuous coding block. It usually contains protein-coding exons and non-coding introns. After DNA is transcribed into pre-mRNA in the...

karyotyping

Chromosome Stains for Detecting Disorders

Chromosome staining helps scientists find genetic disorders by showing the number and physical features of chromosomes. These features appear after DNA condenses into chromosomes during mitosis. Cytogeneticists then stop mitosis and stain the chromosomes to study their banding pattern. The pattern reveals details such as chromosome number, shape, and type. A chromosome description like this is called a karyotype. To create one, scientists take an image of the stained chromosomes and identify...

replication in prokaryotes

How Prokaryotic DNA Is Copied

Prokaryotic DNA is copied through a coordinated process with three main stages: initiation, elongation, and termination. It begins when initiator proteins bind to the single origin of replication, or ori, on the cell’s circular chromosome. The DNA then copies around the circle in both directions, starting from two replication forks, and this produces two DNA molecules. Several proteins work together to open and protect the DNA during replication. Topoisomerase cuts one side of the...

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

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

Transcription and Gene Control

Transcription and gene control explain how cells make RNA from DNA and decide which genes are active. RNA polymerase copies a DNA sequence into RNA, and this is the first step in making a protein from a gene. Many other proteins and control sequences help make messenger RNA, or mRNA, correctly. In eukaryotes, the DNA is first copied into a primary RNA, also called pre-mRNA. This RNA can then be processed into mature mRNA, which serves as the template for protein synthesis. In prokaryotes such...

translation

Protein Synthesis and mRNA Decoding

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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A coleção JoVE Core dá vida à biologia através de mais de 300 vídeos de animação concisos e fáceis de entender que explicam conceitos-chave de biologia, além de mais de 150 vídeos de Cientistas em ação que mostram experimentos reais em pesquisa realizados nos laboratórios atualmente.

Next Generation Science Standards

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Heredity: Inheritance and Variation of Traits

HS-LS3-2

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. ...

Karyotyping

Describing the number and physical features of chromosomes can reveal abnormalities that underlie genetic diseases. This description is facilitated by ...

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 ...

Proofreading

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

Nucleotide Excision Repair

Overview

Exposure to mutagens can damage DNA and result in bulky lesions that distort the double-helix structure or impede proper transcription. Damaged ...

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 ...

Construct an explanation based on evidence for how the structure of DNA determines the structure of proteins which carry out the essential functions of life through systems of specialized cells.

Assessment Boundary: Assessment does not include identification of specific cell or tissue types, whole body systems, specific protein structures and functions, or the biochemistry of protein synthesis.

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structural-organization-of-the-human-body-an-overview

Structural Organization of the Human Body: An Overview

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Develop and use a model to illustrate the hierarchical organization of interacting systems that provide specific functions within multicellular organisms.

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Assessment Boundary: Assessment does not include interactions and functions at the molecular or chemical reaction level.

HS-LS1-2

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Plan and conduct an investigation to provide evidence that feedback mechanisms maintain homeostasis.

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Assessment Boundary: Assessment does not include the cellular processes involved in the feedback mechanism.

HS-LS1-3

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Chromosome Duplication

Cohesins

Condensins

The Mitotic Spindle

Centrosome Duplication

Spindle Assembly

Attachment of Sister Chromatids

Forces Acting on Chromosomes

Separation of Sister Chromatids

Live Cell Imaging of Mitosis

Mitosis is a form of cell division in which a cell&#8217;s genetic material is divided equally between two daughter cells. Mitosis can be broken down into ...

The Spindle Assembly Checkpoint

Cell Division

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Anaphase A and B

Anaphase Promoting Complex

The Contractile Ring

Determining the Plane of Cell Division

The Phragmoplast

Distribution of Cytoplasmic Content

An Introduction to Cell Division

Cell division is the process by which a parent cell divides and gives rise to two or more daughter cells. It is a means of reproduction for single-cell ...

Cell Cycle Analysis

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Use a model to illustrate the role of cellular division (mitosis) and differentiation in producing and maintaining complex organisms.

Assessment Boundary: Assessment does not include specific gene control mechanisms or rote memorization of the steps of mitosis.

HS-LS1-4

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Autotrophs

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The Photochemical Reaction Center

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The Antenna Complex

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the-z-scheme-of-electron-transport-in-photosynthesis

The Z-Scheme of Electron Transport in Photosynthesis

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The Calvin Benson Cycle

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Use a model to illustrate how photosynthesis transforms light energy into stored chemical energy.

Clarification statement: Emphasis is on illustrating inputs and outputs of matter and the transfer and transformation of energy in photosynthesis by plants and other photosynthesizing organisms. Examples of models could include diagrams, chemical equations, and conceptual models.

Assessment Boundary: Assessment does not include specific biochemical steps.

HS-LS1-5

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Lipid-derived Compounds in the Human Body

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Protein Organization

Globular Proteins

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Construct and revise an explanation based on evidence for how carbon, hydrogen, and oxygen from sugar molecules may combine with other elements to form amino acids and/or other large carbon- based molecules.

Clarification statement: Emphasis is on using evidence from models and simulations to support explanations.

Assessment Boundary: Assessment does not include the details of the specific chemical reactions or identification of macromolecules.

HS-LS1-6

DNA Mismatch Repair in Replication

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