- any change in base sequence of DNA

- they are inheritable

-it can lead to a faulty or missing protein

-it can damage somatic cells 

-type of point mutation (90%)

- one base pair is replaced by another

-transition is replacement of a purine w/ a purine or pyrimidine by pyrimidine

-transversion is purine by a pyrimidine

-second most common (9%)

- chromosomal breakage

(if a base is deleted, DNA pol should recognize & fix the problem)

A combination of insertions and deletions

- when one DNA breaks off and inserts on to another DNA

- Generally large and affect many genes

The DNA duplicates

- This happens in Meiosis I during crossing over

the opposite of nonsense

-the stop codon mutates to a different amino acid & keeps translating leading to an extra long amino acid

1. Somatic mutations: aging/cancer

2. Germline mutations: in gametes

- most mutations are harmless

- unfavorable contibute to polygenic

diseases

-children are usually sicker than their parents bc they obtain mutations from parents + those they acquire 

1. Harmless: can persist in the gene pool indefinitely

- frequency is determined by mutation-selection balance

- purifying selection is dominant for disease mutations

2. Detrimental: subject to purifying selection

Dominant

Mutation

Recessive

Mutation

Spontaneous Tautomeric

Shifts

less energy rich & cause mutations in the skin

- it looks like a pyimidine dimer

Chemicals causing

mutation

1. free radicals

2. Base analogs 

- base that is similar to DNA base pair

3. Deaminating Agents

- nitrous acid

4. Alkylating Agents

5. Agents from large adduts

6. Intercalculating Agents

- Planare, aromatic structures that insert themselves between base pairs, pushing them apart

When are most cells sensitive to

mutations?

- Fungal: can stand long and humid conditions

- goes to the liver to be oxidized in order to be excreted

- Epoxide forms leading to liver cancer

Maternal age: increase in age is a risk factor for aberrations in chromosome number

Paternal age: increase in age is a risk factor for point mutations or single-base substitutions

1. 1 or 2 strands are affected

2. locates the piece thats cut

3. excision of damaged region

4. DNA polymerase makes a new strand using the bottom strand as a template

5. DNA ligase seals the nick

the 1st line of defense

- replication errors

Post-Replication

mismatch repair

-gives a heterozygous defect

- replication errors

Mutations in the ATM protein kinase, a signaling protein required for the repair of DNA double-strand breaks

- causes thymus hypoplasia, immunodeficiency/ malignancies/ionizing radiation and diatation of small blood vessels

- A baseless (apurinic) site

- purine gets hydrolyzed from the strand

- it recognize then cuts and recruit pol B to repair the strand

Abnormal Bases

- Base specific

- uses same enzymes as AP endonuclease

bulky lesions

- Genome-wide

- Transcription-coupled

Xeroderma Pigmentosum

- sunburn/ skin cancer/ autosomal recessive

- absence of repair pyrimidine dimers 

Cockayne Syndrome

- Defect of transcription-coupled nucleotide excision repair

- poor growth/ early aging/ autosomal recessive

non-homo & homo end joining

When 1 strand breaks:

-loss of a few nucleotides but prevents chromosome breakage

When 2 strands break:

     - makes an accurate replacement

- looks for homologous chromosome that was broken

(Hereditary nonpolyposis colon cancer)

- defect of post-replication mismatch repair 

- Account for 50% of colon cancer

- Autosomal dominant 

- happens: when a somatic mutation disrupts the single intact copy of the gene