Dna Repair

Front 1

Physical agents of DNA damage

Back 1

a. High temperature
b. Radiation (240-300 nm)
c. UVB
d. X-rays

Front 2

Chemical agents of DNA damage

Back 2

a. Methylating agents
b. Nitrous acid
c. Nitrosamines
d. Acridine dyes

Front 3

DNA damaging agents

Back 3

a. Act by altering structure of DNA
b. Causes disruption of H bonding of complementary base pairs
c. Some cause breaks in the phosphate backbone
d. Each causes a spectrum of damages

Front 4

Altered bases

Back 4

a. Thymine dimer→ best example
b. Two adjacent thymines dimerize
c. Usually due to UV radiation
d. Consequences
i. Inhibition of advance of replication fork

Front 5

Deamination

Back 5

a. Induced or spontaneous loss of an amino group
b. Cytosine→ uracil
c. Adenine→ hypoxanthine

Front 6

Missing bases

Back 6

a. Depurination→ spontaneous loss of a purine
b. 10,000 purines/day/cell
c. “Apurinic site”

Front 7

Strand breaks

Back 7

a. Single strand→ chemical and radiation exposure
b. Double strand→ chemical, particularly anticancer drugs (more lethal)

Front 8

Photoreactivation

Back 8

a. Operates on pyrimidine dimers
b. Exposure of cell to light is essential for repair
c. Does not exist in placental mammals
d. Photolyase
e. Photolyase
i. Catalyzes photoreversal of pyrimidine dimers

Front 9

Excision repair recognition

Back 9

i. Recognition of damaged region→ nicking of DNA at 5’ and 3’ end by a repair endonuclease

Front 10

Excision repair removal

Back 10

ii. Damaged region of DNA is removed and replaced with correct drnMP→ DNA polymerase

Front 11

DNA ligase in excision repair

Back 11

iii. DNA ligase forms phosphodiester bond

Front 12

Requirements for excision repair

Back 12

iv. Requires→ endonuclease, polymerase, ligase

Front 13

Base excision repair-- deamination

Back 13

i. Modification does not disrupt H bonding→ requires activity of another enzyme system→ Uracil DNA glycosylase

Front 14

Uracil DNA glycosylase removal

Back 14

a. Hydrolyzes the bond between uracil and deoxyribose→ removal of uracil from DNA

Front 15

Endonuclease activity in base excision repair-- deamination

Back 15

Removal of uracil results in an apyrimidinic site
b. Apyrimidinic site
i. Results from removal of uracil from DNA by uracil DNA glycosylase
c. Endonuclease recognizes error→ nicking

Front 16

DNA polymerase and ligase in base excision repair-- deamination

Back 16

d. Nick repaired by DNA polymerase and ligase`

Front 17

SOS repair

Back 17

i. Repair enzymes are induced in response to high DNA damage levels
ii. Error prone
iii. Last ditch effort

Front 18

Recombination repair skip

Back 18

ii. DNA polymerase skips thymine dimer and resumes downstream

Front 19

Recombination repair filling in

Back 19

iii. Skip filled in via recombination with the complementary undamaged strand

Front 20

Bacteria recombination protein

Back 20

iv. Bacteria use recA protein to assist in recombination events

Front 21

XP

Back 21

i. Autosomal recessive→ mutation of a single gene
ii. Found on 8 different genetic loci
iii. Mutations in DNA polymerase n→ problem with nicking DNA strand at 5’ end of damaged region

Front 22

Ataxia telangiectasia

Back 22

i. Gamma irradiation sensitivity
ii. Leads to lymphomas
iii. Symptoms:
1. Ataxia
2. Dilation of blood vessels in skin
3. Chromosome aberrations

Front 23

Fanconi's anemia

Back 23

i. Crosslinking agent sensitivity
ii. Leads to leukemia
iii. Symptoms
1. Hypoplastic pancytopenia
2. Congenital anomalies

Front 24

Bloom's syndrome

Back 24

i. UV sensitivity
ii. Leads to leukemia
iii. Photosensitivity

Front 25

Cockayne's syndrome

Back 25

i. UV sensitivity
ii. Patients lack a transcription helicase used in repair→ genes cannot be repair in transcription→ loss of mRNA production
iii. Leads to various tumors
iv. Symptoms:
1. Neurological defects
2. Dwarfism

Front 26

HNPCC

Back 26

i. Hereditary nonpolyposis colorectal cancer
ii. Genes involved in mismatch repair
iii. Mutations in these genes are a strong indicator for cancer
iv. One of most commonly inherited genetic diseases
v. Accounts for 10% of colorectal cancer cases

Front 27

BRCA1/BRCA2

Back 27

i. Linked to hereditary breast and ovarian cancers
ii. Doe for recombination repair proteins linked to Fanconi’s anemia type