2. DNA Replication and Repair Flashcards Preview

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Flashcards in 2. DNA Replication and Repair Deck (37):
1

Polymerases

Enzymes that synthesize nucleic abides by forming PDE bonds, PPi is released

2

Nucleases

Hydrolyze PDE bonds:
- Exonucleases: remove nucleotides from ends
- Endonucleases cut within nucleic acid

3

Required primer DNA polymerase and RNA polymerase

DNA: RNA (or DNA) primer
RNA: None

4

Proofreading activity polymerases

DNA: Yes (exonuclease 3'->5'), RNA: No

5

Helicase

Breaks hydrogen bonds

6

Single stranded DNA binding protein (SSB)

Prevents reassociation of DNA and protects from degradation by nucleases

7

Primase

Synthesizes (10bp) RNA primer

8

DNA polymerase III

Begins synthesizing DNA in 5'->3' direction

9

Leading strand & Lagging strand

Leading = continuously (move to replication fork)
Lagging = Okazaki fragments (move from replication fork)

10

RNAase H + uncharacterized DNA polymerase (delta)

Removes primers in eukaryotes + fills the gap

11

DNA Polymerase I

Removes primers in prokaryotes + fills gap

12

DNA Ligase

Seals the nicks between Okazaki fragments

13

DNA Gyrase (topoisomerase II)

Provides swivel

14

Quinolones, function + examples

Block activity of topoisomerase
Levofloxacin, ciprofloxacin, moxifloxacin

15

Nalidixic acid

Kills bacteria by inhibiting DNA gyrase

16

Etoposide, teniposide

Inhibitors of eukaryotic topoisomerase II

17

Eurkaryotic DNA polymerases

Alfa and delta: leading and lagging strand
Gamma: replicates mitochondrial DNA
Beta and epsilon: DNA repair
Epsilon: can substitute for delta

18

Telomeres

Repetitive sequence at ends of linear DNA

19

Telomerase (only in eukaryotes)

RNA template, reverse transcriptase activity (hTRT). Only present in embryonic cells, germ cells and stem cells, not in somatic cells. Seen in cancer cells

20

Inhbition of reverse transcriptase meds

AZT, ddC and ddI

21

Reverse transcriptase activity in eurkaryotes

- Telomerase (hTRT)
- Retrotransposons (residual viral genomes in human DNA)

22

AZT (HIV treatment)

1. Converted to triphosphate derivative, substrate
2. Azide instead of normal hydroxyl group: prevents further replication by causing chain termination. (Reverse transcriptase does not have proofreading activity)

23

p53

Prevents damaged cells from entering S phase. Associated with Li Fraumeni syndrome and solid tumors

24

ATM

Kinase essential for p53 activity.

25

Ataxia telangiectasia

Inactivated ATM, hypersensitivity to X-rays and predisposition to lymphomas

26

Rb

Retinoblastoma gene, negative regulator cell cycle, binds to E2F and repress transcription of genes

27

Thymine dimers

Caused by UV light

28

Remove thymine dimers

By nucleotide excision-repair mechanism (excision endonuclease, aka excinuclease)

29

Cytosine deamination makes..

Cytosine -> Uracil

30

Removal of uracil by..

Uracil glycosylase enzyme, then recognized by AP endonuclease that removes damaged sequence (loss of purine or pyrimidine)

31

Maintain DNA fidelity in G2

Mismatch repair enzymes MSH2, MLH1

32

Maintain DNA fidelity G1->S

Rb, p53

33

Maintain DNA fidelity in S phase

DNA polymerase proofreading

34

Maintain DNA fidelity in G1/G0 phase

Thymine dimer repair (XP, nucleotide excision repair)

35

Xeroderma pigmentosum (4)

- Autosomal recessive (1/250,000)
- Extreme sensitive to sunlight, skin freckling, ulcerations, skin cancer
- Most common deficiency in excinuclease enzyme
- Measure enzyme level in white blood cells

36

Heriditary nonpolyposis colorectal cancer

- Aka Lynch syndrome
- Deficiency to repair mismatched base pairs (hMLH1 or hMSH2)
- Can inherit one copy, somatic mutation later
- Intestinal cells high cell division rate

37

Microsatellite instability

Short tandem repeats, usually in noncoding regions, e.g. TGTGTG. If mismatch repair lacks, number of repeats at locus will vary.