Lec 7. Diseases associated with defects in DNA replication,repair and recombination

Question 1

What is replication stress?

Answer 1

Defined as slowing or stalling in replication fork progression

Question 2

Pertaining to replication stress from endogenous and exogenous sources, what happens?

Answer 2

Causes genomic instability.

Question 3

What is a Hallmark of Cancer?

Answer 3

Abnormal DNA structures if not resolved can be transmitted to the next gen in the form of DNA lesion resulting in genome instability.

Question 4

What do telomeres do?

Answer 4

Protect the end of chromosomes

Question 5

What happens in short telomere syndromes (STS)?

Answer 5

Accelerated aging by inheritable gene mutations resulting in decreases telomere lengths.

Question 6

What is usually affected with STS?

Answer 6

Organs with high cell turnover, Bone marrow, liver, lungs, and immune systems are commonly affected.

Question 7

What is telomerase?

Answer 7

Enzyme complex (DNA pol) that makes new telomere sequences onto the ends of chromosomes

Question 8

What is DKC (Dyskeratosis congenita)?

Answer 8

Congenital disorder with a highly variable phenotype. Characterized by short telomeres.

Question 9

What are clinical manifestations of DKC?

Answer 9

Abnormal skin pigmentation, nail dystrophy

Question 10

What is a major consequence to DKC?

Answer 10

progressive bone marrow failure.

Question 11

Why is genetic variation critical for evolutionary change?

Answer 11

Adaptation to new environments.

Question 12

What happens in stressful conditions, where adaption might be necessary to survive?

Answer 12

Induce increase mutation in bacteria

Question 13

what are some phenotypes for XP (Xeroderma pigmentosum)?

Answer 13

Skin cancer, UV sensitivity and neuro abnormalities.

Question 14

What enzyme/process is affected with XP?

Answer 14

NER (nucleotide excision repair)

Question 15

What are some phenotypes for AT (Ataxia telangiectasia)?

Answer 15

Leukemia, lymphoma, gamma ray sensitivity, genome instability

Question 16

What enzyme/process is affected with AT?

Answer 16

ATM protein (kinase activated by ds breaks)

Question 17

What are some phenotypes for bloom syndrome?

Answer 17

Cancer, stunted growth and genome instability

Question 18

What enzyme/process is affected with bloom syndrome?

Answer 18

DNA helicase needed for recombination

Question 19

What are the two major DNA repair pathways?

Answer 19

BER and NER

Question 20

What disease is associated with a dysfunctional NHEJ?

Answer 20

SCID

Question 21

True or False? Radiation increases mutation rates in all organisms?

Answer 21

True

Question 22

What does Ionizing radiation do?

Answer 22

Dislodges e- in tissue causes free radicals which damage DNA

Question 23

What does UV light induce?

Answer 23

Formation of pyrimidine dimers. 2 Thymine bases covalently bonded that blocks replication

Question 24

What is the SOS system in bacteria?

Answer 24

Allows bacteria cells to bypass the replication block with a mutation prone pathway.

Question 25

What do oxidative free radicals do?

Answer 25

Convert Guanine into 8-oxy..etc which mispairs with Adenine

Question 26

How does the body repair the formation of pyrimidine dimers (two Thymines)?

Answer 26

Thymine dimer repair (NER). Dimer is repaired by enzymes that cut out the surrounding nucleotides and fill the space back in.

Question 27

What is a good example of mismatch repair defects?

Answer 27

Mutations in the mismatch repair genes (tumer supressor genes) MLH1 and MSH2.

Question 28

What happens when there is a mutation on the MLH1 and MSH2?

Answer 28

These genes get epigenetically turned off and result in microsatellite instability and genomic instability, implicated in some cancers.

Question 29

What is the MGMT gene?

Answer 29

Gene crucial for genome stability. Repairs and prevents mismatch errors during DNA replication and transcription.

Question 30

What are some characteristics for XP?

Answer 30

Sensitive to sunlight, abornmal skin pigmentation.

Question 31

Why is skin cancer likely in XP?

Answer 31

Sunlight exposure produces pyrimidine dimers in skin cell DNA which cant be repaired

Question 32

What repair system tackles UV induced DNA lesions?

Answer 32

NER

Question 33

What is the ATM protein?

Answer 33

a kinase that responds to DNA damage by Phosphorylating key substrates involved in DNA repair and or cell cycle control

Question 34

True or False? ATM mutations carriers that dont have AT are more likely than people without an ATM mutation to develop cancer

Answer 34

True

Question 35

What are diagnosable characteristics for AT?

Answer 35

slurred speech, impaired motor skills and cerebellar dysfunction.

Question 36

What is the most documented function of ATM?

Answer 36

regulating cellular response to DNA ds breaks

Question 37

What are the most common mutations in Bloom Syndrome (BS) pts?

Answer 37

Nonsense or frameshift mutations in the BLM gene that cause trunction of the BLM protein.

Question 38

What are some characteristics of pts with BS?

Answer 38

Small head, redness of cheecks, DM

Question 39

What are RecQ helicases?

Answer 39

They unwind DNA for preparation of replication

Question 40

How are BLM and BRCA 1&2 related?

Answer 40

BML works in combination with BRCA 1&2, all involved in DNA repair and talk with each other