Mammalian DNA Replicaiton and Telomeres

Question 1

Similarities between mammalian and E. Coli replication

Answer 1

Similar replication fork geometry

Multiprotein replication machine

Question 2

Differences between E. Coli and mammalian DNA replication

Answer 2

E. Coli: Single origin of replication and same polymerase for leading and lagging strand synthesis

Mammalian: Multiple origins of replication and same or different polymerases for leading and lagging strand synthesis

Question 3

Function of DNA polymerase alpha

Answer 3

Primase

Question 4

Function of DNA polymerase beta

Answer 4

Repair

Question 5

Function of DNA polymerase gamma

Answer 5

Mitochondrial replication

Question 6

Function of DNA polymerase delta

Answer 6

Nuclear replication

Question 7

Function of DNA polymerase epsilon

Answer 7

Nuclear replication

Question 8

Function of RNaseH

Answer 8

Enzyme that degrades RNA part of an RNA/DNA hybrid

Question 9

There is no polymerase that performs ___ activity

Answer 9

3’ to 5’ activity

Question 10

What end of DNA shortens after each replicaition cycle?

Answer 10

5’ end

Question 11

What are the consequences of the shortening of DNA after each cycle?

Answer 11

Coding sequences may be eventually lost

Senescence or death signal may be triggered

Question 12

Chromosome Replication and Stable propagation require

Answer 12

Origins of replication (Ori or ARS)

Centromere

Telomere

Question 13

What is the function of telmoeres

Answer 13

Seal the ends of chromosomes

Prevents undesirable fusion

Prevents aberrant recombination

Attach chromosomes to nuclear envelope

Facilitate replication

Question 14

Telomeres have

Answer 14

Hexameric repeats

Question 15

What are the hexameric repeats of telomeres?

Answer 15

TTAGGG/TTGGGG

Question 16

What is telomerase?

Answer 16

Ribonucleoprotein (RNP) = Protein + RNA

Question 17

What is the function of the protein part of telomerase: RNP

Answer 17

Reverse transcriptase (RNA dependent DNA polymerase)

Question 18

What is the structure and function of the RNA part of telomerase: RNP

Answer 18

150 nucleotides long

Functions as a template

Question 19

How is the G-tail of telomeres created

Answer 19

By limited digestion of CA strand

Question 20

How do telomeres protect chromosome ends?

Answer 20

The four G bases on the same strand stack up by base pairing

Question 21

What cells have no detectable activity of telomerase?

Answer 21

Somatic cells (differentiated cells)

Question 22

What cells show detectable activity of telomerase?

Answer 22

Germ cells/stem cells

Tumors

Question 23

Length of telomeres serves as a

Answer 23

Mitotic clock

Question 24

Shortened telomeres induce

Answer 24

Replicative senescense

Apoptosis

Question 25

Therapeutic applications of telomeres- targets for intervention

Answer 25

Telomerase activity Telomere structure

Question 26

What is a telomerase inhibitor and how does it work?

Answer 26

GRN163L Is a competitive inhibitor binding to active site of enzyme

Question 27

What is RHPS4

Answer 27

G-quadruplex ligand- stabilizes the G-quadruplex and prevents attachement of telomerase

Question 28

What is the function of GRN163L and RHPS4

Answer 28

Block the replicative potential of cancer cells

Question 29

What is a virion?

Answer 29

An inert virus particle outside of the cell host

Question 30

Replication of viruses involves

Answer 30

Synthesis of genome Transcription of genome Translation

Question 31

Viral genomes are variable in

Answer 31

Size, organization, and replication patterns

Question 32

Some common viral processes include

Answer 32

Replication Packaging Host cell alternations for efficient propagation of viruses

Question 33

Genome of HIV

Answer 33

Two identical copies of 9749 nucleotide RNA

Question 34

Replication of RNA requires __ which is done by __

Answer 34

Viral RNA --> DNA Done by priming by tRNA-lys and cDNA formation by reverse transcriptase

Question 35

What is reverse transcriptase?

Answer 35

RNA dependent DNA polymerase

Question 36

Integration of cDNA copy of viral RNA into the host genome is done by

Answer 36

Integrase

Question 37

Which is more prone to error, reverse transcriptase or DNA polymerase?

Answer 37

Reverse transcriptase

Question 38

What are the targets of inhibition of HIV?

Answer 38

Fusion Reverse transcriptase Protease Integrase

Question 39

What is zidovudine

Answer 39

ZDV/AZT An analogue of deoxythymidine Antimetabolite drug used to treat AIDS

Question 40

How does Zidovudine/AZT work?

Answer 40

Prevents DNA chain elongation by reverse transcriptase because it lacks a 3' OH group

Question 41

Replication of HIV can be inhibited by?

Answer 41

Impairment of or interference with the activity of various enzymes involved in DNA replication Limiting the supply of substrates by inhibiting the synthesis of dATP, dCTP, dGTP, dTTP

Question 42

HIV: inhibitors of bacterial gyrase are used as ___

Answer 42

Antibiotics

Question 43

HIV: inhibitors of human topoisomerase are used for

Answer 43

Chemotherapy

Question 44

HIV: inhibitors of synthesis of dATP, dCTP, dGTP, and dTTP are used for

Answer 44

Chemotherapy

Question 45

What is 5-Florouracil

Answer 45

Inhibitor of DNA replication Used for cancer chemotherapy

Question 46

How does 5-Florouracil inhibit DNA synthesis

Answer 46

By inhibiting thymidyalte synthase (an enzyme for TMP synthesis)

Question 47

How is 5-Florouracil created?

Answer 47

Capecitabine (Xeloda) = orally administered chemotherapeutic agent that is convered to fluorouracil in the body

Question 48

5-Florouracil is an analogue of

Answer 48

Uracil or Thymine