TOPIC 5 BS1030: MECHANISMS OF MUTATIONS

What does DNA stand for?

Deoxyribonucleic Acid

What is the primary function of DNA?

It contains all the genetic information needed for the structure, function, and regulation of cells.

Describe the structure of DNA.

DNA has a double helix structure, often compared to a twisted ladder.

How many strands does DNA have?

Two strands running in opposite directions (antiparallel).

What are the repeating units of DNA called?

Nucleotides.

What are the components of a nucleotide?

A phosphate group, a deoxyribose sugar, and a nitrogenous base.

List the four DNA bases.

Adenine (A), Thymine (T), Cytosine (C), Guanine (G).

What is the significance of base pairing in DNA?

It is essential for DNA replication, accurate genetic inheritance, and repair mechanisms.

Which bases pair together in DNA?

Adenine pairs with Thymine (2 hydrogen bonds) and Cytosine pairs with Guanine (3 hydrogen bonds).

What keeps DNA stable and protected?

Hydrogen bonds between base pairs and stacking interactions between bases.

What are some sources of DNA damage?

Environmental agents (UV radiation, X-rays, chemicals) and natural processes (DNA replication errors, reactive oxygen species).

Why is DNA repair essential?

Unrepaired DNA damage can lead to mutations, cancer, genetic diseases, and cell death.

What can mutations in DNA lead to?

Disruption of protein function, altered regulation, and abnormal cell behavior.

How can DNA damage cause cancer?

Mutations can affect genes controlling cell division, DNA repair, and apoptosis.

What is an example of DNA damage caused by UV radiation?

Thymine dimers, which can lead to melanoma and other skin cancers.

What happens if DNA damage occurs in eggs or sperm?

It can cause hereditary conditions.

What can severe DNA damage trigger in a cell?

Apoptosis (cell death).

What is the role of reactive oxygen species in DNA damage?

They can cause damage during natural processes inside the cell.

What is a common result of DNA replication errors?

DNA lesions that can lead to mutations.

What is the impact of smoking chemicals on DNA?

They can cause base modifications leading to lung cancer.

What does DNA integrity refer to?

The completeness, accuracy, and undamaged state of the DNA molecule.

What are the three main aspects of DNA integrity?

1. DNA is intact 2. DNA sequence is correct 3. DNA remains stable.

What does it mean if DNA is intact?

There are no breaks in the sugar-phosphate backbone, no missing bases, and no chemical modifications.

What indicates a correct DNA sequence?

The order of bases (A, T, C, G) has not changed and no mutations have occurred.

What contributes to DNA stability?

Intact hydrogen bonds between base pairs and a structurally sound double helix.

What is the consequence of high DNA integrity?

DNA is undamaged, accurate, and stable.

What does low DNA integrity indicate?

DNA has been altered, damaged, or mutated.

Why is DNA integrity important for cells?

Cells depend on DNA to produce proteins, enzymes, hormones, and cell structures.

What can happen if DNA is damaged?

The wrong proteins may be made, disrupting normal cell function and potentially leading to diseases like cancer.

What are some potential outcomes of DNA damage?

Accumulation of mutations, errors in cell division, genetic instability, and developmental disorders.

What are some repair systems that maintain DNA integrity?

Base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair.

What types of damage do DNA repair systems prevent?

Damage from UV radiation, free radicals, replication errors, and chemical toxins.

What happens if DNA repair fails?

DNA integrity drops, which can lead to dysfunction or disease.

What is DNA damage?

Physical or chemical harm to the DNA molecule, such as broken bonds or modified bases.

What is a DNA mutation?

A permanent change in the DNA nucleotide sequence.

Why does DNA damage not always lead to mutation?

Cells have efficient DNA repair systems that detect and fix damage, resulting in fewer than 1 in 1,000 DNA lesions becoming mutations.

What is mutagenesis?

The process by which mutations occur, including natural errors during DNA replication and mutations caused by environmental agents.

What are harmful mutations?

Mutations that disrupt normal gene function and can cause diseases, such as many cancers and inherited disorders.

Give an example of a harmful mutation.

Cystic fibrosis or BRCA1/BRCA2 cancer mutations.

What are beneficial mutations?

Rare mutations that can improve survival or reproduction and provide raw material for evolution.

Give an example of a beneficial mutation.

Sickle cell trait providing resistance to malaria.

What are neutral mutations?

Mutations that have no obvious effect and make up most mutations in the genome.

What are small-scale mutations?

Mutations that affect one or a few nucleotides, including point mutations, insertions, and deletions.

What are frameshift mutations?

Mutations caused by insertions or deletions that change the reading frame of the genetic code.

What are large-scale mutations?

Mutations that affect chromosomes, including duplications, deletions, translocations, and inversions.

What is a mutagen?

Any physical or chemical agent that increases the rate of mutation.

Name a physical mutagen.

UV radiation, which can cause thymine dimers and lead to skin cancer.

Name a chemical mutagen.

Cigarette smoke or nitrous acid.

What are biological mutagens?

Viruses that insert their genetic material into host DNA, potentially causing mutations.

What is the role of DNA repair systems?

To detect damage, remove faulty parts, and restore the correct DNA sequence.

What percentage of DNA damage is typically repaired?

99.9% of DNA damage is fixed.

What types of mutations can occur during DNA replication?

Natural errors that can lead to mutations.

What can large-scale mutations lead to?

Major genetic disorders.

What is the significance of mutations in evolution?

They provide genetic variation that can be acted upon by natural selection.

What are spontaneous mutations?

Genetic changes that occur naturally, without any external mutagen, due to random chemical changes in DNA.

What is depurination?

The loss of a purine base (adenine or guanine) from DNA, leading to an apurinic site which can cause replication errors.

What is deamination?

The removal of an amino group from a base, converting it into a different base, such as cytosine to uracil.

What is tautomerism?

A temporary change in the chemical form of a DNA base that can lead to incorrect base pairing during replication.

What causes spontaneous mutations?

They arise from internal chemical processes, such as thermal energy and natural chemical instability of DNA.

What are exogenous sources of DNA damage?

Environmental factors that damage DNA, including ionizing radiation, free radicals, UV radiation, mutagenic chemicals, and anti-cancer drugs.

How does ionizing radiation damage DNA?

It causes double-strand breaks, base loss, and chromosome rearrangements, significantly increasing cancer risk.

What are free radicals?

Highly reactive molecules that can cause base modifications, strand breaks, and crosslinks in DNA.

What types of damage does UV radiation cause?

It causes thymine dimers, distorts the DNA helix, and blocks DNA replication, potentially leading to skin cancers.

What are mutagenic chemicals?

Chemicals that directly damage or alter DNA, such as alkylating agents and certain toxins found in food.

How do anti-cancer drugs damage DNA?

They intentionally crosslink DNA, break strands, and block replication to stop cancer cell division.

What are endogenous sources of DNA damage?

Damage that occurs inside the cell during normal physiological processes, including replication errors and reactive oxygen species.

What are replication errors?

Mistakes made during DNA replication, such as mismatched base pairs, insertions, or deletions.

What are reactive oxygen species (ROS)?

Molecules produced naturally in cells that can cause base oxidation and strand breaks in DNA.

What is the significance of spontaneous mutations?

They can lead to harmful effects like base substitutions, mismatches, frameshifts, genetic diseases, and cancer if not repaired.

What happens if deamination is not repaired?

Cytosine pairs with uracil instead of guanine, leading to a mutation in the DNA sequence.

How frequently does cytosine deamination occur?

Approximately 1 in 10 million cytosines deaminate every 24 hours, resulting in about 100 deaminations per day in each cell.

What is an apurinic site?

A site in DNA where a purine base has been lost due to depurination, which can lead to replication errors.

What are the consequences of frameshift mutations?

They can lead to significant changes in the protein sequence, potentially resulting in dysfunctional proteins.

What is the effect of thermal energy on DNA?

It can contribute to spontaneous mutations by causing random chemical changes in the DNA structure.

What is the relationship between DNA damage and cancer?

DNA damage, especially in tumor suppressor genes or DNA repair genes, can lead to the development of cancer.

What are the three major categories of DNA damaging agents?

Ionising radiation, Ultraviolet radiation, Mutagenic chemicals, and DNA replication errors.

What types of radiation are included in ionising radiation?

X-rays, gamma rays, and radioactive particles.

How does ionising radiation damage DNA?

It ejects electrons, causing DNA strand breaks and ring opening.

What are the two types of DNA strand breaks caused by ionising radiation?

Single-strand breaks (SSBs) and double-strand breaks (DSBs).

Why are double-strand breaks (DSBs) particularly dangerous?

They can cause chromosome rearrangements and cancer.

What is the main type of damage caused by ultraviolet (UV) radiation?

Pyrimidine dimers, particularly thymine dimers.

How do pyrimidine dimers affect DNA?

They bend the DNA and hinder proper reading by DNA polymerase, leading to replication errors.

What are free radicals and how do they damage DNA?

Free radicals are reactive oxygen species that can cause base oxidation, single-strand breaks, double-strand breaks, and sugar modifications.

What is an example of a mutagenic chemical and its mechanism?

Dimethyl sulfate (DMS) is an alkylating agent that adds methyl groups to bases, causing incorrect base pairing and point mutations.

What are intercalating agents and their effect on DNA?

Intercalating agents like ethidium bromide insert between DNA bases, causing DNA polymerase to slip, leading to insertions or deletions.

What types of mutations can result from intercalating agents?

Frameshift mutations, which change all downstream codons.

What is a transition mutation?

A mutation where a purine swaps with a purine or a pyrimidine swaps with a pyrimidine.

What is a transversion mutation?

A mutation where a purine swaps with a pyrimidine.

What is replication fork slippage?

It occurs when DNA polymerase temporarily slips on the template, causing loops that lead to insertions or deletions.

What genetic disease is linked to replication fork slippage?

Huntington's disease, due to CAG expansions.

What is the role of DNA replication in genetic variation?

It produces two identical DNA copies, allowing for mutations that contribute to evolution.

What is the consequence of too many errors during DNA replication?

Cell death.

What is the consequence of too few errors during DNA replication?

Lack of genetic variation, which is necessary for evolution.

What is an abasic site in DNA?

A site where a DNA base has been removed, often due to ionising radiation damage.

What are mutations?

Permanent changes in the DNA sequence.

At what levels can mutations occur?

Nucleotide level, gene level, and chromosome level.

What must happen for DNA damage to become a mutation?

The damage must be left unrepaired.

What are germline mutations?

Mutations that occur in gametes (sperm or egg) and are inherited by offspring.

What are somatic mutations?

Mutations that occur in body cells and are not inherited.

What is a missense mutation?

A point mutation that results in a different amino acid being coded for.