Name: fixing dna copying errors
Uploaded: 2020-11-23T11:47:35.000Z
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

heredity-inheritance-and-variation-of-traits

Heredity: Inheritance and Variation of Traits

HS-LS3-2

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 repair

<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.

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

Molecular Biology

Moleculaire biologie

Unit 1

DNA Replication

DNA-replicatie

KEY TERMS AND CONCEPTS

BELANGRIJKE TERMEN EN CONCEPTEN

Mismatchesreparatie

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 not work well, the mistake can remain in the DNA. That can raise the chance of mutation over time. For this reason, mismatch repair is an important safeguard during DNA replication.

Fixing DNA Copying Errors

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 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

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.

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

Learn how mismatch repair fixes DNA copying errors after replication and uses mutator proteins to detect, remove, and replace mismatched bases.

Fixing DNA Copying Errors | JoVE K12

molecular biology

JoVE Core Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

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

The DNA Helix

The Central Dogma

Mutations

genome-size-and-the-evolution-of-new-genes

Genome Size and the Evolution of New Genes

While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major ...

Gene Families

Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes ...

types-of-genetic-transfer-between-organisms

Types of Genetic Transfer Between Organisms

Genetic transfer occurs when genetic information is passed from one organism to another. It occurs via two mechanisms: vertical gene transfer and ...

DNA Packaging

DNA as a Genetic Template

Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The ...

Organization of Genes

Chromosome Structure

A functional eukaryotic chromosome must contain three elements: a centromere, telomeres, and numerous origins of replication.
The centromere is a DNA ...

Chromosome Replication

Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone ...

Karyotyping

Euchromatin

The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions ...

Heterochromatin

chromatin-position-affects-gene-expression

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the ...

Ask questions to clarify relationships about the role of DNA and chromosomes in coding the instructions for characteristic traits passed from parents to offspring.

Assessment Boundary: Assessment does not include the phases of meiosis or the biochemical mechanism of specific steps in the process.

HS-LS3-1

What is Meiosis?

Meiosis I

Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of ...

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for ...

Meiosis vs. Mitosis

Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, ...

Crossing over

Nondisjunction

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a ...

Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and ...

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this ...

Nucleotide Excision Repair

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide ...

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the ...

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages ...

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of ...

Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors.

Clarification statement: Emphasis is on using data to support arguments for the way variation occurs.

Assessment Boundary: Assessment does not include the phases of meiosis or the biochemical mechanism of specific steps in the process.

Pedigree Analysis

Overview

A pedigree is a diagram displaying a family&#x2019;s history of a trait. Analyzing pedigrees can reveal (1) whether a trait is dominant or ...

Probability Laws

Overview

The probability of inheriting a trait can be calculated using the sum and product rules. The sum rule is used to calculate the probability of ...

Hardy-Weinberg Principle

Diploid organisms have two alleles of each gene, one from each parent, in their somatic cells. Therefore, each individual contributes two alleles to the ...

Hardy-Weinberg and Genetic Drift

Evolutionary change is interesting and important to study, but changes in populations occur over long periods of time and in huge physical spaces and are ...

Apply concepts of statistics and probability to explain the variation and distribution of expressed traits in a population.

Clarification statement: Emphasis is on the use of mathematics to describe the probability of traits as it relates to genetic and environmental factors in the expression of traits.

Assessment Boundary: Assessment does not include Hardy-Weinberg calculations.

HS-LS3-3

Fixing DNA Copying Errors

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