DNA Damage And Repair

Question 1

what are some short term consequences of DNA damage?

Answer 1

Reduced proliferation, altered gene expression,and apoptosis

Question 2

What are some long term results of DNA damage?

Answer 2

Aging and cancer/other diseases

Question 3

What is the difference between DNA damage and DNA mutations?

Answer 3

DNA damage occurs a lot, but is usually repaired. DNA mutations are the result of DNA damage not being recognized and being replicated

Question 4

What are the two types of spontaneous mutations?

Answer 4

Errors or replication and spontaneous lesions

Question 5

Errors of Replication

Answer 5

Mistakes made during replication. Only occur during the S phase of cell division.

Question 6

Spontaneous Lesions

Answer 6

Chemical changes that occur spontaneously and occur in the resting cell

Question 7

Tautomerism

Answer 7

Ability of certain chemicals to exist as a mixture of two interconvertible isomers (e.g., thymine has an enol form that can pair with G and its normal form which pairs with A)

Question 8

What is the exonuclease activity of DNA polymerase?

Answer 8

3’—>5’

Question 9

Bloom Syndrome

Answer 9

Defect in the BLM gene which is a DNA helicase enzyme, causing the DNA to not be properly unwound. This results in many chromosomal breaks and sister chromatid exchanges.

Question 10

What are some symptoms of Bloom syndrome?

Answer 10

Small, narrow chin and prominent ears/nose, facial rash upon exposure to the sun, diabetes and immune system defects

Question 11

Fanconi Anemia

Answer 11

Autosomal Recessive rare disorder. Multiple genes are involved in the disorder (locus heterogeneity), all genes are in the FANC family which are related to DNA repair. Disease causes spontaneous chromosome breakage and increased risk of neoplasia

Question 12

What are some symptoms of Fanconi anemia?

Answer 12

radial Ray defects, mental development problems, and short stature.

Question 13

Frameshift Mutations

Answer 13

Tend to occur at positions where there are base repeats. DNA loops are kinks at these points and some of the bases are not copied or are copied twice.

Question 14

Spontaneous Lesions

Answer 14

Changes that occur in a resting cell due to the chemical nature of DNA. Very common, and increased by exposure to mutagens. Three main types are depurination, deamination, oxidative damage.

Question 15

Depurination

Answer 15

Most common spontaneous lesion. Caused by breaking of glycosidic bond between base and sugar in purine nucleotides

Question 16

Deamination

Answer 16

Second most common spontaneous lesion. Loss of amine group from a base (usually cytosine) which deaminates to form uracil. This one is easy to fix because your body knows that you don’t want uracil in DNA

Question 17

Which deamination is hard to detect?

Answer 17

5-methyl cytosine can deaminate to thymidine which results in a mutation hotspot because your body doesn’t know which nucleotide is the right one. This is seen frequently in the CG islands

Question 18

Oxidative damage

Answer 18

Results from the production of reactive oxidative compounds due to oxidative metabolism. This causes a mis-pairing with A and a potential transversion.

Question 19

What kind of damage does UV light cause?

Answer 19

Can form covalent linkages between bases on the same strand which will interfere with normal pairing and block replication.

Question 20

Nucleotide Excision

Answer 20

Remove about 30 bases around a damaged site. Repairs pyrimidine diners formed by UV damage

Question 21

Base Excision

Answer 21

Repairs a single (or just a few) damaged bases by removing it (when it’s damaged by methylation, oxidation, etc)

Question 22

Mismatch Repair

Answer 22

Post replication repair. Repairs mismatched bases that were formed due to tautomerism.

Question 23

Steps to excision repair

Answer 23

1) Damage recognized
2) Endonucleases are recruited
3) regain is excised
4) DNA polymerase fills gaps
5) ligase seals the nick

Question 24

Xeroderma Pigemetosum (XP)

Answer 24

Mutations in 9 different NER genes can lead to XP. Locus heterogeneity that causes extreme sun sensitivity. DNA damage is cumulative and irreversible.

Question 25

How are damaged bases removed in base excision repair?

Answer 25

Removed by DNA glycosylases which can recognize specific damaged bases.

Question 26

Steps to mismatch repair

Answer 26

1) Mismatch is recognized by MMR proteins
2) repair may occur during S-phase or in G2 when the genome is scanned for errors.
3) Excision of bases around mismatch repair
4) Repair by re-synthesis

Question 27

Hereditary Nonpolyposis Colon Cancer

Answer 27

result of mutations in genes encoding mismatch repair proteins (MSH2 and MLH1) which results in microsatellite instability

Question 28

Double Stand break

Answer 28

Very difficult to repair and is dangerous to dividing cells.

Question 29

What are the two types of repair for double strand DNA breaks?

Answer 29

Non-homologous end joining-more common

Recombinantional repair-uses homologous chromosomes, less error prone than NHEJ

Question 30

BRCA1 and BRCA2

Answer 30

Found in breast and other tissue. Involved in DNA repair or apoptosis when it can’t be repaired. Shows alleluia heterogeneity.

Question 31

Ataxia Telangiectasia

Answer 31

Defect in ATM which is protein kinase with a number of functions that include detecting DNA damage and activating DNA repair proteins (p53). Very rare autosomal recessive disease.