DNA Repair and Human Diseases

Question 1

In base excision repair, what enzyme helps recognize the non-bulky DNA lesion and excise it out

Answer 1

Bifunctional DNA glycosylases

Question 2

enzyme that helps in the resynthesis of DNA strand during base excision repair

Answer 2

polymerases

Question 3

enzyme that is used in the end process step (ligation) of base excision repair

Answer 3

Ligases

Question 4

DNA glycosylase mutation that is caused by mutation in MUTYH gene

patients have colon polyps and increased risk for colon cancer

Answer 4

MAP

(MUTYH Associated Polyposis)

Question 5

DNA glycosylase mutation that is caused by mutation in NTHL1 gene

transition mutation in carcinomas

Answer 5

NAP

(NTHL1 Associated Polyposis)

Question 6

during DNA replication in humans, what gets replicated

Answer 6

the whole genome

Question 7

this DNA repair happens during post-replication

Answer 7

DNA Mismatch Repair

Question 8

goal of this repair is post-replicative mutation avoidance and to maintain genome stability

Answer 8

DNA Mismatch repair

Question 9

cells that are deficient in this type of repair are highly mutagenic

Answer 9

DNA Mismatch Repair

Question 10

repeated sequences of DNA

ex. CGG repeats, CAG repeats, TTAGG

Answer 10

microsatellites

Question 11

site on DNA strand where most mutations happen (Polymerase gets confused and moves on)

Answer 11

microsatellites

Question 12

these 2 proteins are important in DNA Mismatch repair and recognize the lesion and recruit another helper (protein)

Answer 12

MutSα
(MSH6 and MSH2)

Question 13

proteins recruited by MSH6 and MSH2 to help in recognizing lesion and removing it

Answer 13

MutLα
(PMS2 and MLH1)

Question 14

this syndrome is caused by heterozygous mutations in MSH6, MSH2, PMS2, and MLH1

Answer 14

Lynch Syndrome

Question 15

autosomal dominant and leads to 2-7% of colorectal cancers in US; caused by 1 bad allele

Answer 15

Lynch Syndrome

Question 16

what two protein mutations are the most common in causing Lynch syndrome

Answer 16

MSH2/MLH1

Question 17

type of DNA Repair that has a lot of clinical significance- majority of diseases are involved with this repair

Answer 17

Nucleotide Excision Repair (NER)

Question 18

2 ways that nucleotide excision repair is initiated:

Answer 18

global genome repair (GGR)-longer path
transcription coupled repair (TCR)-shorter path

Question 19

the 4 R’s of Repair:

Answer 19

Recognize
Remove
Replace
Restore

Question 20

repair step in any DNA repair is always performed by what enzyme

Answer 20

polymerase

Question 21

this DNA repair system involves BULKY adducts (helix distorting)

Answer 21

Nucleotide Excision Repair (NER)

Question 22

UV light, cancer drugs (cisplatin) and cigarette smoke cause this type of lesion

Answer 22

helix-distorting (NER lesion) (bulky adducts)

Question 23

this repair system includes these steps: Endonuclease cleaves the phosphate backbone upstream and downstream the mismatch –> Exonuclease removes segment of damaged strand –> Polymerase fills gap with new nucleotides–>Ligase seals bonds and damage is repaired

Answer 23

DNA Mismatch repair(MMR)

Question 24

DNA mismatch repair deficiency that is super rare and caused by having 2 bad alleles

Answer 24

Constitutional mismatch repair

Question 25

recessive genetic disorder that is caused by extreme sensitivity to sunlight and increased risk of skin cancer; mutation in NER

Answer 25

Xeroderma Pigmentosum (XP)

Question 26

disease that arises from mutations in XPA-XPG of nucleotide excision repair

Answer 26

XP

Question 27

NER disease that is caused by mutations in CSA or CSB

Answer 27

Cockayne Syndrome (CS)

Question 28

this NER disease includes sx’s of photosensitivity, growth failure, retinal degeneration

NO skin cancer

Answer 28

CS

Question 29

very rare disorder that is caused by mutations in TFIIH subunits (XPB, XPD, XPG)

combination of clinical features (will still have risk of skin cancer)

Answer 29

Combined XP-CS

Question 30

this NER disease results from mutations in XPB, XPD, or TTDA

photosensitivity and NO skin cancer

Answer 30

TTD (trichothiodystrophy)

Question 31

NER disease resulting in mutation in ERCC1

death or developmental failure

Answer 31

COFS syndrome

Question 32

NER syndrome that includes kyphosis (curvature of spine), vision loss, cachexia (break down muscle for energy), and NO cancer is involved

Answer 32

XFE (XPF-ERCC1) progeroid syndrome

Question 33

this DNA repair is the most potent DNA damage (most deleterious damage) due to ionizing radiation

Answer 33

Double Strand Break Repair (DSB)

Question 34

this pathway of DSB doesn’t use sister chromatid; repair DNA breaks by direct ligation- prone to error

Answer 34

NHEJ

Question 35

this type of DSB repair uses sister chromatids an dDNA polymerases fix the lost genetic material; leads to faithful re-creation of the original sequence
ex. BRCA2 uses RAD51 to ssDNA to catalyze homologous pairing

Answer 35

HR (homologous recombination)

Question 36

DNA damage sensors of double stranded DNA breaks

Answer 36

ATM and ATR

Question 37

mutations in ATM lead to this disease
sx’s: leukemia, lymphoid malignancies, impaired gait and red spots, neurodegeneration, immunodeficiency

Answer 37

Ataxia Telangiectasia (A-T)

Question 38

mutation in ATR that causes this disease
sx’s: sensitivity to UV radiation, present w/ dwarfism, microencephaly

Answer 38

Seckel Syndrome

Question 39

this syndrome is caused by mutation in NBS1/P95; causes hypersensitivity to ionizing radiation and microcephaly

null mutations of MRE complex lethal in mammalian cells

Answer 39

NBS (nijmegen breakage syndrome)

Question 40

this disease is caused by mutations in FANCA and FANCV; uses several repair pathways (NER, TLS, HR, interstrand crosslink repair); bone marrow failure and cancer

Answer 40

Fanconi Anemia (FA)

Question 41

helicase disorder (no BLM helicase functioning) that is autosomal recessive and has solid and hematologic malignancies; stunted growth

Answer 41

Bloom Syndrome

Question 42

helicase disorder (no WRN helicase functioning) that causes a person to look older than they actually are; genomic instability

Answer 42

Werner Syndrome

Question 43

gene that deals with breast and ovarian cancer

Answer 43

BRCA2