Mutations and Repair

Question 1

What usually results in mutation?

Answer 1

Failure to repair/repair accurately lesions to the DNA.

Question 2

Do mutations permanently alter the sequence of bases in a gene?

Answer 2

Yes

Question 3

What happens where there are mutations in prokaryotes?

Answer 3

The mutation affects only one copy of the genetic information and if the organism survives it will be passed on to the next generation.

Question 4

Can mutations in germ cells in multicellular organisms be transmitted?

Answer 4

Yes they can to subsequent generations. (I.e. cancer)

Question 5

What are somatic mutations?

Answer 5

They are mutations that affect tissues (cancer) but are not heritable.

Question 6

How do eukaryotic cells react when there is damage to DNA?

Answer 6

The cell cycle arrests until repairs are completed. If too extensive apoptosis may be triggered. Tissue damage safer than risk of cancer.

Question 7

How do prokaryotes react to DNA damage?

Answer 7

Cell cycle arrests and is followed by emergency repair via SOS systems. Many cells die but some mutants survive because cannot afford to lose entire population.

Question 8

When are somatic mutations harmful?

Answer 8

If they result in a substantial clone of mutant cells (i.e. tumor or mutation in embryogenesis at progenitor cells)

Question 9

Why do we get cancer?

Answer 9

Some mutations increase mutation rate

Some mutations enhance cell proliferation

Question 10

What are the four major types of mutation?

Answer 10

Substitution
Deletion
Insertion
Rearrangement

Question 11

Do mutations tend to occur together or apart?

Answer 11

Deletion, Insertion and Rearrangements tend to occur together (i.e. radiation)

Question 12

What are the types of substitution mutations?

Answer 12

Silent
Missense
Nonsense
Frameshift

Question 13

Transition vs. Transversion Substitutions

Answer 13

Transition = purine for purine/pyrimidine for pyrimidine
Transversion = purine for pyrimidine/pyrimidine for purine

Question 14

What is the most common mutation in cystic fibrosis?

Answer 14

Deletion of one codon (Phe out 1480)

Question 15

What are 4 causes of mutations?

Answer 15

1) Errors during DNA replication (substitutions)
2) Chemical modification (substitutions)
3) Intercalation of certain chemical mutagens between cases (insertions and deletions)
4) Double stranded breakage and “emergency repair” (rearrangements and deletions)

Question 16

What is intercalation?

Answer 16

Distorts helix which can block DNA replication and RNA transcription
Believed to interfere with any ongoing repair

Question 17

How does radiation cause mutations?

Answer 17

X-ray exposure causes double stand breaks in DNA resulting in rearrangements and deletions

UV exposure causes thymine dimers that interfere with replication

Question 18

What does mismatch repair do?

Answer 18

Repairs mismatches

Question 19

What does base-excision repair do?

Answer 19

Repairs abnormal bases, alkylated bases and pyrimidine dimers

Question 20

What does nucleotide-excision repair?

Answer 20

DNA lesions that cause large structural changes

Question 21

What does direct repair repair?

Answer 21

Pyrimidine dimers

Question 22

How is the correct strand chosen in mismatch repair?

Answer 22

In prokaryotes DNA is methylated at GATC sites which provides a temporary tag for parent strand as replication fork passes through
This guide excision of the daughter instead of the parent strand

Question 23

What do mismatch repair defects lead too?

Answer 23

Leads to a strong predisposition to cancer (i.e. hereditary nonpolyopsis colorectal cancer)

Question 24

What enzyme do all cells have that remove abnormal bases in a DNA strand?

Answer 24

DNA glycosylases

Question 25

How does base excision repair work?

Answer 25

Enzymes remove base but leave sugar intact creating an AP site > specific AP endonuclease cuts sugar out > repair system fills in gap

Question 26

How does nucleotide excision repair work?

Answer 26

Bulky distortions (thymine dimers) are removed (by ABC exonuclease in E. coli) then repair system fills the gap

Question 27

What happens in nucleotide excision repair defects?

Answer 27

Leads to an autosomal recessive disease Xeroderma pigmentosum

Question 28

What are the symptoms of xeroderma pigmentosum?

Answer 28

High sensitivity to skin damage by UV light

Strong predisposition to skin cancer

Question 29

What happens in infancy with xeroderma pigmentosum?

Answer 29

Skin becomes dry and dermis atrophies
Keratoses form, eyelids scar and cornea ulcerates
Multiple skin tumors form and many patients die before the age of 30 from metastasis

Question 30

How does direct repair work?

Answer 30

Repair without removing a base or nucleotide
Energetically expensive (dealkylating alkylated bases)

Question 31

Example of low energy cost direct repair

Answer 31

Pyrimidine dimers can be repaired by light induced reverse reaction catalyzed by photolyases (less cost, no chance for more mistakes)

Question 32

What alkylation agent should you know?

Answer 32

Mustard gas

Question 33

What is the phenotype of Hereditary nonpolyopsis colorectal cancer?

Answer 33

Colon cancer

Question 34

What repair process is affected in hereditary nonpolyopsis colorectal cancer?

Answer 34

Mismatch repair

Question 35

What repair process is affected in zeroderma pigmentosum?

Answer 35

Nucleotide excision-repair