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Flashcards in Chapter 2 Deck (41)
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1
Q

What is semiconservative replication?

A

when parental strands are used as template for synthesis of a new complementary strand

2
Q

What are the properties of bacterial replication?

A
  1. single origin of replication
  2. bidirectional process –> two identical circular molecules of DNA
3
Q

What are the properties of eukaryotic replication?

A
  1. multiple origins of replication
  2. bidirectional replication produces two identical linear mocelcules of dsDNA (sister chromatides)– in nucleas during S phase
4
Q

What is a polymerase?

A

enzyme that synthesizes nucleic acids by forming a phosphodiester bond (PDE)

5
Q

What is a nuclease? What are the two types?

A

enzymes that hydrolyze PDE bonds

  1. exonuclease: remove nucleotides from 5’ or 3’ end
  2. endonucleases: cut within the nucleic aicd and release nucleic acid fragments
6
Q

What are the two types of exonucleases?

A
  1. 3’ exonuclease: proofreading of DNA polymerase, S phase
  2. 5’ exonuclease = removes RNA primer, S phase
7
Q

What is the difference between DNA and RNA synthesis?

A
  1. DNA polymerase binds to RNA primer (laid down by primase)

RNA doesn’t require a primer

  1. DNA uses dNTP nto dNMP as substrate (PPi released)

RNA uses NTP as substrate (PPi released)

  1. DNA polymerases proofread (3’–>5’ exonuclease) = high fidelity

RNA polymerase doesn’t proofread = low fidelity

  1. DNA contains thymine

RNA contains uracil

8
Q

What are the similarities of DNA and RNA synthesis?

A
  1. DNA and RNA polymerase read template 3’–>5’
  2. DNA and RNA synthesized 5’–>3’
  3. newly synthesized strand is complementary and antiparallel to template strand
  4. Pyrophosphate (PPi) released during reaction
9
Q

Steps of DNA replication.

A
  1. base sequence of origin of replication recognized
  2. helicase breaks hydrogen bonds
  3. single-stranded DNA binding protein (SSB) prevents strands from reassociating and protects them from degredation
  4. primase makes short RNA primer
  5. DNA polymerase III syntehsizes DNA (leading strand v. lagging strand and Okazaki fragments)
  6. RNA primers removed by RNAase H and DNA polymerase fills the gaps

(in prokaryotes, DNA polymerase I removes primer (5’ exonuclease) and makes new DNA

  1. DNA ligase seals nicks between Okazaki fragments
  2. DNA gyrase (DNA topoisomerase II) inserts negative supercoils
10
Q

What does DNA topoisomerase II do?

A

removes positive supercoils ahead of advancing replication forks

Work in G1 cells

11
Q

What drugs block the action of topoisomerases?

A

Quinolones, Fluoroquinolones: most active against aerobic gram-negative bacteria

ex. Nalidixic acid: kills bacteria by inhibiting DNA gyrase

Levofloxacin, Ciprofloxacin, Moxifloxacin

Treats: gonorrhea, upper and lower urinary tract infections

12
Q

Why don’t drugs that inhibit prokaryotic topoisomerase II (gyrase) also inhibit eukaryotic topoisomerase II?

A

these enzymes have the same catalytic properties but different biochemistry

13
Q

What drug inhibits eukaryotic topoisomerase II?

A

Etoposide, teniposide: antineoplastic

Anticancer agents

14
Q

What are the side effects and why?

A

Don’t affect most cells becuase they are in G0 phase

Cells that are in G1 phase acted on and lead to side effects

Ex. Hair loss, digestive problems

15
Q

What are telomeres?

A

repetitive sequences at the ends of linear DNA molecules in eukarytoic chromsomes

shortened with each round of replication (aging of cells)

16
Q

What is a telomerase?

A

enzyme that maintains telomeres

short RNA template complementary to DNA telomere sequence and telomerase reverse transcriptase activity

17
Q

Where are telomerases present?

A

embryonic cells, fetal cells, cetain adult stem cells

not present in adult somatic cells

cancer cells–contributing to unlimited replication

18
Q

What is the action of the HIV drug AZT?

A

incorporated into DNA and causes chain termination

HIV has reverse transcriptase that is DNA polymerase but doesn’t have proofreading activity

19
Q

What are the side effects of AZT?

A

AZT inhibits reverse transcriptase activity of HIV but also reverse transcriptase activity of telomerase in G1 stage cells

20
Q

Which cells have increase telomerase activity?

A

Cancer cells, normal embryonic cells

21
Q

What is a disease with decreased telomerase activity

A

**Progeria **

Rapid aging in children

22
Q

What are the tumor suppressor genes?

A

p53, ATM, BRCA 1 and 2 and Rb

23
Q

What is the action of p53?

A

encodes a protein that prevents cell with damaged DNA from entering S phase

24
Q

What is Li Fraumeni syndrome?

A

inactivation or deletion of p53

causes many solid tumors

25
Q

What does the ATM gene do?

A

encodes kinase essential for p53 activity

26
Q

What is ataxia telangiectasia?

A

inactivation of ATM gene

hypersensitivity to x-rays and predisposition to lymphomas

27
Q

How does the retinoblastoma (Rb) gene work?

A

negative regulator of cell cycle

binds to transcription factor E2F and represses the transcription of genes required for S phase

28
Q

What are the three types of DNA repair?

A
  1. repair of thymine dimers
  2. mismatch repair
  3. base excision repair: cytosine deamination
29
Q

When does thymine dimer damage occur and what is the cause?

A

G1 phase

UV radiation

30
Q

How are thymine dimers recognized/excised and repaired?

A

Recognized/excised: excision endonuclease

Repaired: DNA polymerase and ligase

31
Q

What enzyme is deficient in Xeroderma pigmentosum?

A

excision endonuclease–can’t excise thymine dimers (interfere with DNA replication and normal gene expression)

Autosomal recessive disorder

32
Q

What are the symptoms of Xeoderma pigmentosum (XP)?

A

Extreme UV sensitivity

Excessive freckling

Multiple skin cancers

Corneal ulcerations

33
Q

What cancers are common for patients with Xeroderm pigmentosum in early life?

A

Carcinoma and melanoma

34
Q

How can xeroderma pigmentosum be diagnosed?

A

measurement of enzyme excision endonuclease in white blood cells of blood

35
Q

What is hereditary nonpolyposis colorectal cancer (HNPCC)?

A

Lynch syndrome

mutation in hMSH2 or hMLH1 intitiates defective repair of DNA mismatches

leads to DNA instability because no H-bonds

36
Q

Why does mimatched bases occur?

A

DNA replication errors

37
Q

When do mismatched bases occur?

A

G2 phase

38
Q

How are mismatched bases recognized/excised and repaired?

A

Recognized/excised: hMSH2, hMLH1

Repair: DNA polymerase and ligase

39
Q

What is microsatellite instability?

A

microsatellites are di-, tri- and tetranucleotide repeates throughout DNA (usually in non-coding regions)

Cells without mismatch repaire will varry in the number of repeast of microsatellites at llocus

Variation–>microsatellite instability

40
Q

When does cytosine deamination occur and what causes it?

A

G1 phase

Spontaneous, heat, nitrates (meat preservatives)

[cytosine–>uracil]

41
Q

What recognizes/excises and repaires cytosine deamination?

A

Recognize/repair: uracil glycosylase AP endonuclease

Repair: DNA polymerase and ligase