DNA Replication and Repair

Question 1

Significant features of Origins of Replication?

Answer 1

Rich in A-T base pairing, makes it easier to unwind

Question 2

What prevents 2 unwound DNA strands from annealing back together thru complementary base pairing?

Answer 2

Single-strand DNA binding proteins

Question 3

Secondary function of SSDBPs?

Answer 3

Protect ssDNA from DNase nuclease activity

Question 4

Function of Ciprofloxacin?

Answer 4

• wide spectrum bacterial antibiotic topoisomerase inhibitor

Question 5

Function of Irinotecan and Topotecan?

Answer 5

• Type I topoisomerase inhibitors
• used to tx colorectal and ovarian cancer
• inhibit ligation step

Question 6

Function of Doxorubicin (adriamycin), etoposide, and ellipticine?

Answer 6

• Type II topoisomerase inhibitors

- tx many types of cancer

Question 7

What is a processive polymerase? Example?

Answer 7

• can cont long stretches of DNA synth w/o falling off

- DNA Pol III

Question 8

DNA Pol I function

Answer 8

• synth of short stretches of DNA on lagging strand

- fills in mature Okazaki fragments & removes primers

Question 9

Function of DNA Pol alpha

Answer 9

• synth RNA primers w/ RNTs

Question 10

Function of DNA Pol delta

Answer 10

• lagging strand synth

Question 11

Function of DNA Pol epsilon

Answer 11

• leading strand synth

Question 12

Function of DNA Pol beta

Answer 12

• repairs damaged DNA

Question 13

What proteins remove RNA primers in eukaryotes?

Answer 13

• complex containing FEN-1 and RNAse H

Question 14

Why are telomerase inhibitors used in cancer tx?

Answer 14

• cancer cell lines become immortal by activation of telomerase activity

Question 15

Function of AZT in HIV tx

Answer 15

• thymidine analog that replaces 3’-OH group w/ 3’-azide group
• terminates strand for HIV RT
• prevents viral replication

Question 16

Function of DDI in HIV tx

Answer 16

• purine analog
• hydrogen @ 2’- and 3’-carbons
• causes chain termination

Question 17

What viruses does Acyclovir treat? (3)

Answer 17

• herpes simplex
• varicella zoster (chickenpox)
• herpes zoster (shingles)

Question 18

What is Gancyclovir used to treat?

Answer 18

• cytomegalovirus (CMV) retinitis (blindness)

Question 19

Mechanism of Gancyclovir and Acyclovir? (4)

Answer 19

• guanosine analogs
• guanosine phosphorylated in infected cells by viral kinase
• drugs incorporated into viral genome
• prevent replication

Question 20

What does cytosine form after deamination?

Answer 20

Uracil

Question 21

When is Base Excision Repair (BER) used?

Answer 21

• when damage results in change in a base on 1 strand of DNA duplex

Question 22

Deamination of 5-methylcytosine leads to ?

Answer 22

Thymine

Question 23

When is Nucleotide Excision Repair (NER) used?

Answer 23

• when damage –> larger lesions in DNA (eg thymidine dimers from UV)

Question 24

NER mechanism? (4)

Answer 24

• XP-C or Rad23B recognize bulge in DNA
• recruitment of DNA helicase activity (TFIIH)
• XP-F and XP-G endonucleases remove path around lesion
• DNA pol repairs region

Question 25

Function of Cisplatin? (3)

Answer 25

- anti-cancer drug - causes DNA adduction - DNA damage should kill cancerous cells thru apoptosis

Question 26

Clinical implication of XP-F (ERCC1)?

Answer 26

- confers resistance to Cisplatin

Question 27

When is Mismatch Excision Repair (MER) used?

Answer 27

- corrects errors not caught during replication that cause mismatched BPs

Question 28

Cause of hereditary nonpolyposis colorectal cancer?

Answer 28

- mutation in a copy of MLH1 or MSH2 (supposed to detect mispairing)

Question 29

Cause and effect of Xeroderma pigmentosum?

Answer 29

- cause: defect in an NER gene --> inability to globally repair UV damaged DNA - effect: predisposed to cancer

Question 30

Cause and effect of Cockayne syndrome?

Answer 30

- cause: defect in transc-coupled repair | - effect: neuro defects and premature aging

Question 31

What 2 genes are mutated in Cockayne syndrome?

Answer 31

1. ERCC8 (interacts w/ TFIIH) | 2. ERCC6 (helicase)

Question 32

Most common use of BER?

Answer 32

Fixing 5MeC to T mutation

Question 33

Most common use of NER?

Answer 33

Fixing thymidine dimer mutation