L6 dna damage and mutation

What is DNA damage

A change to the chemical structure of DNA

What types of structural changes count as DNA damage

Backbone breaks base loss base alteration and mismatches

What is a mutation

A heritable change in DNA sequence

Can mutations be repaired

No

Can DNA damage be repaired

Yes

What happens if DNA damage is replicated

It can become a mutation

What is a point mutation

Change in one or a few bases

What is a chromosome mutation

Large scale rearrangement deletion or insertion

Are DNA damage and mutation the same

No

What is a transition mutation

Purine to purine or pyrimidine to pyrimidine change

What is a transversion mutation

Purine to pyrimidine or vice versa

What is a silent mutation

Base change with no amino acid change

What is a missense mutation

Base change leading to different amino acid

What is a conservative mutation

Amino acid change to similar type

What is a non conservative mutation

Amino acid change to different type

What is a forward mutation

Wild type to mutant

What is a reverse mutation

Mutant back to wild type

What is true reversion

Restores original sequence

What is partial reversion

Restores function without original sequence

What is a suppressor mutation

Second mutation that compensates first

Where can suppressor mutations occur

Same gene or different gene

Are most mutations spontaneous

Yes

What is mutation rate in prokaryotes

About one in a billion nucleotides per generation

What is germline mutation rate in eukaryotes

About one in one hundred million nucleotides per generation

What is somatic mutation

Mutation in body cells

What is a major driver of cancer

Somatic mutation

Are mutations adaptive

No they are random

What experiment showed mutations are random

Luria Delbruck experiment

What are two theories of mutation origin

Adaptive and random

What causes spontaneous mutations

Replication errors and endogenous damage

What is tautomerism

Rare base forms causing mismatches

What is replication slippage

Looping out leading to insertions or deletions

Why must replication be accurate

To prevent permanent mutations

What is a premutagenic lesion

A mismatch that can become mutation

How do tautomers cause mutation

They pair incorrectly during replication

What happens if mismatches are not repaired

Permanent mutation occurs

What is depurination

Loss of purine base from DNA

What is an AP site

DNA site with no base

How many depurination events occur daily in cells

Around 18000

What does an AP site cause during replication

Random substitution or deletion

What is deamination

Removal of amino group from base

What does cytosine deamination produce

Uracil

Why is uracil in DNA abnormal

It is normally not present

What does deamination of methyl cytosine produce

GT mismatch

What sequences are mutation hotspots

CpG sequences

What is alkylation

Addition of alkyl group to DNA base

What molecules can cause alkylation

Endogenous donors or external agents

What effect does alkylation have

Alters base pairing

What causes oxidative DNA damage

Reactive oxygen species

What bases are commonly affected by oxidation

Guanine

What is 8oxoG

Oxidised guanine base

What can oxidative damage lead to

Mutation or strand breakage

Why are mitochondrial genomes prone to mutation

High oxidative damage

What are mutagens

Agents that increase mutation rate

What are types of mutagens

Chemical and physical

What is an example of a physical mutagen

UV radiation

What is an example of chemical mutagen

Base analog

What is a base analogue

Molecule similar to DNA base

What does 5 bromouracil cause

Transition mutations

What does nitrous acid do

Deaminates bases

What does hydroxylamine do

Hydroxylates bases

What does MMS do

Methylates bases

What are intercalating agents

Molecules that insert into DNA helix

What is an example of intercalating agent

Ethidium bromide

What mutations do intercalating agents cause

Insertions and deletions

What is a frameshift mutation

Insertion or deletion altering reading frame

Why do intercalating agents cause frameshifts

They distort DNA structure

What are polycyclic aromatic hydrocarbons

Chemicals requiring activation to damage DNA

What activates these hydrocarbons

Cytochrome p450 enzymes

What reactive compounds are produced

Epoxides

What is the overall effect of DNA damage

It can lead to mutations

Can DNA damage come from internal sources

Yes

Can DNA damage come from external sources

Yes

What types of internal damage exist

Deamination oxidation alkylation and replication errors

What types of external damage exist

Chemical and physical mutagens