Mammalian DNA Replicaiton and Telomeres Flashcards Preview

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Flashcards in Mammalian DNA Replicaiton and Telomeres Deck (48)
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1
Q

Similarities between mammalian and E. Coli replication

A

Similar replication fork geometry

Multiprotein replication machine

2
Q

Differences between E. Coli and mammalian DNA replication

A

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

3
Q

Function of DNA polymerase alpha

A

Primase

4
Q

Function of DNA polymerase beta

A

Repair

5
Q

Function of DNA polymerase gamma

A

Mitochondrial replication

6
Q

Function of DNA polymerase delta

A

Nuclear replication

7
Q

Function of DNA polymerase epsilon

A

Nuclear replication

8
Q

Function of RNaseH

A

Enzyme that degrades RNA part of an RNA/DNA hybrid

9
Q

There is no polymerase that performs ___ activity

A

3’ to 5’ activity

10
Q

What end of DNA shortens after each replicaition cycle?

A

5’ end

11
Q

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

A

Coding sequences may be eventually lost

Senescence or death signal may be triggered

12
Q

Chromosome Replication and Stable propagation require

A

Origins of replication (Ori or ARS)

Centromere

Telomere

13
Q

What is the function of telmoeres

A

Seal the ends of chromosomes

Prevents undesirable fusion

Prevents aberrant recombination

Attach chromosomes to nuclear envelope

Facilitate replication

14
Q

Telomeres have

A

Hexameric repeats

15
Q

What are the hexameric repeats of telomeres?

A

TTAGGG/TTGGGG

16
Q

What is telomerase?

A

Ribonucleoprotein (RNP) = Protein + RNA

17
Q

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

A

Reverse transcriptase (RNA dependent DNA polymerase)

18
Q

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

A

150 nucleotides long

Functions as a template

19
Q

How is the G-tail of telomeres created

A

By limited digestion of CA strand

20
Q

How do telomeres protect chromosome ends?

A

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

21
Q

What cells have no detectable activity of telomerase?

A

Somatic cells (differentiated cells)

22
Q

What cells show detectable activity of telomerase?

A

Germ cells/stem cells

Tumors

23
Q

Length of telomeres serves as a

A

Mitotic clock

24
Q

Shortened telomeres induce

A

Replicative senescense

Apoptosis

25
Q

Therapeutic applications of telomeres- targets for intervention

A

Telomerase activity

Telomere structure

26
Q

What is a telomerase inhibitor and how does it work?

A

GRN163L

Is a competitive inhibitor binding to active site of enzyme

27
Q

What is RHPS4

A

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

28
Q

What is the function of GRN163L and RHPS4

A

Block the replicative potential of cancer cells

29
Q

What is a virion?

A

An inert virus particle outside of the cell host

30
Q

Replication of viruses involves

A

Synthesis of genome

Transcription of genome

Translation

31
Q

Viral genomes are variable in

A

Size, organization, and replication patterns

32
Q

Some common viral processes include

A

Replication

Packaging

Host cell alternations for efficient propagation of viruses

33
Q

Genome of HIV

A

Two identical copies of 9749 nucleotide RNA

34
Q

Replication of RNA requires __ which is done by __

A

Viral RNA –> DNA

Done by priming by tRNA-lys and cDNA formation by reverse transcriptase

35
Q

What is reverse transcriptase?

A

RNA dependent DNA polymerase

36
Q

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

A

Integrase

37
Q

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

A

Reverse transcriptase

38
Q

What are the targets of inhibition of HIV?

A

Fusion

Reverse transcriptase

Protease

Integrase

39
Q

What is zidovudine

A

ZDV/AZT

An analogue of deoxythymidine

Antimetabolite drug used to treat AIDS

40
Q

How does Zidovudine/AZT work?

A

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

41
Q

Replication of HIV can be inhibited by?

A

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

42
Q

HIV: inhibitors of bacterial gyrase are used as ___

A

Antibiotics

43
Q

HIV: inhibitors of human topoisomerase are used for

A

Chemotherapy

44
Q

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

A

Chemotherapy

45
Q

What is 5-Florouracil

A

Inhibitor of DNA replication

Used for cancer chemotherapy

46
Q

How does 5-Florouracil inhibit DNA synthesis

A

By inhibiting thymidyalte synthase (an enzyme for TMP synthesis)

47
Q

How is 5-Florouracil created?

A

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

48
Q

5-Florouracil is an analogue of

A

Uracil or Thymine