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

Some errors in DNA replication, such as incorrect base pairing between adenine and cytosine, can remain even after proofreading. Cells fix these errors after replication through a process called mismatch repair.During mismatch repair, proteins detect distortions in DNA caused by mispaired bases. In bacteria, one of these proteins is MutS.Other mismatch repair proteins, such as MutL, help distinguish the newly synthesized DNA strand from the original template strand, ensuring that only the incorrect strand is targeted for repair.Different organisms identify the new DNA strand in different ways. In E. coli, the parental DNA strand is already methylated, while the newly synthesized strand remains temporarily unmethylated, allowing mismatch repair proteins to recognize and repair this new strand.In eukaryotes, the newly synthesized DNA strand often contains small breaks, called nicks. Mismatch repair proteins recognize these nicks and target that strand.Once the incorrect strand is identified, exonuclease enzymes remove a section of DNA that contains the error.DNA polymerase then fills in the missing nucleotides, and DNA ligase seals the remaining gaps, restoring the correct DNA sequence.

mismatch repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.<h4>The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair</h4>The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic information needs to be replicated. Despite the proofreading ability of the DNA polymerase, a copying error occurs approximately every 1 million base pairs. One type of error is the mismatch of nucleotides, for example, the pairing of A with G or T with C. Such mismatches are detected and repaired by the Mutator protein family. These proteins were first described in the bacteria Escherichia coli (E. coli), but homologs appear throughout prokaryotes and eukaryotes.Mutator S (MutS) initiates the mismatch repair (MMR) by identifying and binding to the mismatch. Subsequently, MutL identifies which strand is the new copy. Only the new strand requires fixing while the template strand needs to remain intact. How can the molecular machinery identify the newly synthesized strand of DNA?<h4>Newly Synthesized Strands of DNA Differ from Their Template Strand</h4>In many organisms, cytosine and adenine bases of the new strand receive a methyl group some time after replication. Therefore, Mut proteins identify new strands by recognizing sequences which have not yet been methylated. Additionally, the newly synthesized strand in eukaryotes is more likely to have small breaks, also called DNA nicks. The MMR proteins can thus identify the nicked strand and target it for repair.After identification of the new strand, nuclease enzymes cut the affected region and excise the incorrect nucleotides. Next, DNA polymerase fills in the correct nucleotides and DNA ligase seals the sugar-phosphate backbone of the DNA, thereby completing the mismatch repair process.<h4>Defects in the Mismatch Repair Mechanism Can Cause Cancer</h4>The human homolog of MutS is called Mutator S homolog 2 (MSH2). If MSH2 function is compromised, point mutations and frameshift mutations throughout the genome are not properly repaired. In consequence, humans carrying a single copy of such a compromised MSH2 have a higher likelihood of developing cancer.<h4>Unrepaired Mutations Fuel Adaptation</h4>Would it be best if MMR never missed a mismatch? Even low mutation rates can cause a problem for an organism. However, mutations also contribute to genetic variation in a population. For instance, a permissive mismatch repair system in a bacterium can, by chance, lead to the mutation of a gene that confers antibiotic resistance, thereby increasing the chances of bacterial survival and reproduction when exposed to antibiotics. This is great news for the bacterial population, but bad news for humans that rely on antibiotics to combat infectious diseases.In fact, Staphylococcus aureus strains increasingly gain multidrug-resistance, meaning that few or no antibiotics can prevent the spread of this bacterium in a patient. Infections with multidrug-resistant bacteria are associated with a high mortality rate in humans. The widespread usage of antibiotics in livestock production and inappropriately shortened administration of antibiotics contribute to the emergence of multidrug-resistant bacteria.

Overview

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

https://cloudfront.jove.com/files/ftp_upload/10791/10791_article_thumb_10791.jpg

Education

JoVE Core

Biology

Genetics

DNA Structure and Function

KEY TERMS AND CONCEPTS

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...

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

JoVE Core series brings biology to life through over 300 concise and easy-to-understand animated video lessons that explain key concepts in biology, plus more than 150 scientist-in-action videos that show actual research experiments conducted in today’s laboratories.

biology

Next Generation Science Standards

heredity-inheritance-and-variation-of-traits

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.

Characteristics of Life

Biology is a natural science that studies life and living organisms, including their structure, function, development, interactions, evolution, ...

https://cloudfront.jove.com/files/media/science-education/science-education-thumbs/10647.jpg

Levels of Organization

Biological organization is the classification of biological structures, ranging from atoms at the bottom of the hierarchy to the Earth&#x27;s biosphere. ...

Overview of Anatomy and Physiology

Human anatomy is the scientific study of the body&#39;s structures. Some of these structures are very small and can only be observed and analyzed with the ...

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

Structural Organization of the Human Body: An Overview

It is convenient to consider the body&#39;s structures in terms of fundamental levels of organization that increase in complexity: subatomic particles, ...

Functions of Life

Human life is characterized by a variety of functions that are essential for survival and well-being. These functions include metabolism, movement, ...

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

Clarification statement: Emphasis is on functions at the organism system level such as nutrient uptake, water delivery, and organism movement in response to neural stimuli. An example of an interacting system could be an artery depending on the proper function of elastic tissue and smooth muscle to regulate and deliver the proper amount of blood within the circulatory system.

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

HS-LS1-2

Requirements for Human Life

The Earth and its atmosphere have provided humans with air, water, and food, but these are not the only requirements for survival. Humans also require a ...

What is Homeostasis?

Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, ...

Negative and Positive Feedback

Homeostatic Imbalance

Homeostasis is the maintenance of a stable internal environment within the body, which is crucial for the proper functioning of cells, tissues, organs, ...

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

Clarification statement: Examples of investigations could include heart rate response to exercise, stomate response to moisture and temperature, and root development in response to water levels.

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

HS-LS1-3

What is the Cell Cycle?

The cell cycle refers to the sequence of events occurring throughout a typical cell&#8217;s life. In eukaryotic cells, the somatic cell cycle has two ...

Interphase

The cell cycle occurs over approximately 24 hours (in a typical human cell) and in two distinct stages: interphase, which includes three phases of the ...

The Cell Cycle Control System

Positive Regulator Molecules

Inhibition of CDK Activity

Mitogens and the Cell Cycle

Mitosis and Cytokinesis

In eukaryotes, the cell division cycle is divided into distinct, coordinated cellular processes that include cell growth, DNA replication/chromosome ...

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

Cell division is fundamental to all living organisms and required for growth and development. As an essential means of reproduction for all living things, ...

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

Cell cycle refers to the set of events through which a cell grows, replicates its genome, and ultimately divides into two daughter cells through the ...

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

Photosynthesis

Autotrophs

Almost all living organisms on Earth depend on photosynthesis, which is the process that converts sunlight energy into a simple sugar called ...

What is Photosynthesis?

All living organisms on Earth are directly or indirectly dependent on photosynthesis. It is the only biological process that can capture energy from ...

The Anatomy of Chloroplasts

Green algae and plants, including green stems and unripe fruit, harbor specialized organelles called chloroplasts to carry out photosynthesis. They ...

Photosystems

Photosystems are multiprotein complexes that form the functional units of photosynthesis in plants, algae, and cyanobacteria. They are found embedded in ...

The Photochemical Reaction Center

Reaction centers are pigment-protein complexes that initiate energy conversion from photons to chemical entities. Therefore, photochemical reaction center ...

The Antenna Complex

Plants and other photosynthetic organisms comprise pigments capable of absorption of direct sunlight. These pigments are present in the reaction center - ...

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

The Z-Scheme of Electron Transport in Photosynthesis

The light reactions of photosynthesis assume a linear flow of electrons from water to NADP+. During this process, light energy drives the splitting of ...

The Calvin Benson Cycle

Ribulose 1,5- bisphosphate carboxylase/oxygenase (RuBisCo) is a critical enzyme that catalyzes carbon dioxide assimilation during photosynthesis. However, ...

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

Compounds Essential to Human Function

The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all ...

Overview of Functional Groups

Functional groups are a group of atoms with characteristic properties, which when linked to the carbon skeleton of a molecule, alter the properties of ...

Introduction to Carbohydrates

Carbohydrates, proteins, and fats are the primary macronutrients in the human diet. However, carbohydrates are the most favored source of energy in the ...

Carbohydrate Metabolism

Sugars as Energy Storage Molecules

What are Lipids?

lipid-derived-compounds-in-the-human-body

Lipid-derived Compounds in the Human Body

Fats and lipids are crucial components in the human body. Some lipid-derived compounds, such as fat-soluble vitamins, eicosanoids, lipoproteins, and ...

Fats as Energy Storage Molecules

What are Proteins?

Protein Organization

Globular Proteins

In organisms, proteins are the most abundant macromolecules. They act as the building blocks of life and play various crucial roles in the body. Proteins ...

Fibrous Proteins

Fibrous proteins are either long and narrow proteins or assemble to form long and thin structures. They contain repetitive units and usually consist of ...

Protein Denaturation

The function of proteins depends on their native three-dimensional structure, which is dictated by the amino acid sequence of the specific protein. ...

Role of Proteins in the Human Body

Proteins are the building block of life. They are also&#160; the most abundant macromolecules with as many diverse roles in the body. They are part of ...

Nucleic Acids and Nucleotides

Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell&#39;s genetic blueprint and have instructions for its ...

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

Description

Transcript

Tags

More videos by Standards