FTM 62 - DNA Repair

Question 1

What are the common short term and long term consequences of DNA damage?

Answer 1

Short Term - reduced cell proliferation, altereed gene expression, cell death

Long Term - aging, disease (especially cancer)

Question 2

What are the two types of mutations that occur?

Answer 2

Spontaneous

Induced

Question 3

What are the two classes of spontaneous mutation?

Answer 3

Errors of replication (only occur during S phase)

Spontaneous lesions (chemical changes that can occur whenever)

Question 4

What is the example of nucleotide tautomerism we need to know?

Answer 4

Thymine, which normally pairs with “A” can convert into a tautomer that pairs with “G”

Question 5

What is the error rate of DNApol? What is it actually thanks to proof-reading?

Answer 5

1/100,000 bases

1/10,000,000 bases

Question 6

What causes Bloom Syndrome? What are its symptoms? What are its long term implications?

Answer 6

Question 7

What causes Fanconi anemia? What are its symptoms and long term implications?

Answer 7

Fanconi anemia is a very rare autosomal recessive disease many different genes (up to 8) are mutated. Most of those genes encode proteins needed for DNA repair. Fanc A (there is Fanc A-H) causes 65% of cases. These mutations cause increased spontaneous chromosome breakage which is made worse by exposure to DNA cross linking agents. Symptoms are radial ray defects (underdevelopment of radius bone), pancytopenia (deficiency of red cells, white cells, and platelets), mental delay, and short stature. There is a significantly increased risk of neoplasia.

Question 8

Where do frameshift mutations tend to occur? What is thought to cause these mutations? Why?

Answer 8

Question 9

How often do spontaneous DNA lesions occur?

Answer 9

tens of thousands per cell per day

Question 10

What are the three main types of spontaneous DNA lesions?

Answer 10

Depurination

Deamination

Oxidative damage

Question 11

What is the most common form of spontaneous DNA lesion?

Answer 11

Depurination, it occurs about once every 10 seconds in every cell

Question 12

What are the purines and pyrimidines?

Answer 12

Purines - adenine and guanine

Pyrmidines - cytosine, thymine, and uracil

Question 13

Facts to know about deamination

Answer 13

• Occurs about 500 times per cell per day
• Loss of amine group from base, particularly cytosine
• Cytosine deaminates to form uracil, however, 5-methyl cytosine deaminates to thymidine
• The uracil transformation is easy to recognize because uracil doesn’t belong in DNA but the thymidine transformation could result in the wrong base being repaired
• Because of this, methylated cytosine is considered a mutational hotspot

Question 14

Facts to know about oxidative damage to DNA.

Answer 14

Question 15

Facts to know about DNA damage from UV light

Answer 15

Question 16

Describe the basics of DNA excision repair

Answer 16

Question 17

What does nucleotide excision repair do?

Answer 17

Removes up to about 30 bases around a damaged site and fills it back in

Question 18

What does base excision repair do?

Answer 18

Repairs a single (sometimes a few) damaged base by removing it

Question 19

What does mismatch repair do?

Answer 19

It repairs mismatched bases that formed due to tautomerism or erroneous replication.

Question 20

What type of repair mechanisms are used to fix DNA damage caused by methylation, UV damage, oxidation, tautomeric shifts, and repeat expansions?

Answer 20

UV damage is repaired by nucleotide excision repair

Methylation and oxidation is repaired by base excision repair

Tautomeric shifts and repeat expansions are repaired by mismatch repair

Question 21

What causes Xeroderma pigmentosum? What are its symptoms and long term implications?

Answer 21

XP is caused by an autosomal recessive mutation one or more of 9 different nucleotide excision repair genes. This leads to extreme sun sensitivity, conjunctivitis, and ocular tumors. Long term XP causes a 1000 fold increase in the risk of skin cancers and 20% of affected individuals have progressive neurologic degeneration

Question 22

Describe how single nucleotide base excision repair occurs.

Answer 22

Question 23

At what point in the cell cycle does mismatch repair occur?

Answer 23

Right after replication or in G2 when genome is scanned for errors

Question 24

How does mismatch repair happen?

Answer 24

Question 25

During mismatch repair, how does a cell know which strand is the correct strand?

Answer 25

Question 26

Facts to know about hereditary Nonpolyposis Colon Cancer?

Answer 26

Question 27

What are the two mechanisms for repairing double stranded DNA breaks? Which method is more common? Which method is more accurate? Which method uses the homologous chromosome?

Answer 27

Question 28

Facts to know about the BRCA proteins/genes.

Answer 28

Question 29

Answer 29

Question 30

What are the two primary consequences of mutations to DNA repair genes?

Answer 30

Question 31

What causes Ataxia telangiectasia? What are its symptoms?

Answer 31

Ataxa telangiectasia is caused by a rare autosomal recessive mutation of the ATM gene which codes for a serine threonine kinase responsible for detecting DNA damage and activating cell cycle arrest and DNA repair proteins. This diseas affects the cerebellum (ataxia) and immune system as well as increasing the incidence of cancer. Ocular telangiectasia is common