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Molecules to Cells > DNA Replication in Eukaryotes > Flashcards

DNA Replication in Eukaryotes Flashcards

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Organic Chemistry 101 flashcards
1
Q

What is the eukaryotic version of helicase?

A

MCM

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2
Q

What is one difference about the replication fork/complex in eukaryotes?

A

A pre-replication complex (pre-RC) must form on ARS (origin of rep) before helicase can act

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3
Q

More Pre-RC are ______ (assembled) than _______ (used).

A

Licensed

Fired

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4
Q

What causes Meier-Gorlin Syndrome?

A

Mutations in genes that encode the proteins required for the the Pre-RC complex.

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5
Q

What are symptoms of Meier-Gorlin syndrome?

A

Failture to thrive
Patella hypoplasia
Small upper and lower jaw

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6
Q

What causes DK?

A

Defective telomerase/telomere shortening

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7
Q

What is unique about telomerase?

A

It contains a reverse transcriptase component

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8
Q

Why are telomeres needed?

A

The lagging strand gets left with a left over primer that when removed, would shorten the DNA. Telomerase replaces the gap.

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9
Q

How does telomerase work?

A

It positions itself at the end, add a telomere repeat, reposition, etc.

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10
Q

Do telomerases use DNA or RNA?

A

RNA

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11
Q

In order to protect itself telomeres…

A

Loop back on themselves and create a t-loop and a d-loop

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12
Q

What are symptoms of DK?

A 
Premature aging
Oral leukoplakia
Skin hyperpigmentation
Nail dystrophy/ridging
Bone marrow failure/aplastic anemia
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13
Q

What is Hoyeraal-Hreiderasson (H-H) syndrome?

A

Rare variant of DK

Diagnosed in first months

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14
Q

What are the symptoms of H-H syndrome?

A

Aplastic anemia
Severe immunodeficiency
Cerebellar hypoplasia
Mutation in hTERT, hTR

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15
Q

Disease of telomere shortening show anticipation due to loss of telomerase function in _____ cells.

A

Germ

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16
Q

What are the two major methylated bases in prokaryotes?

A

Adenine and Cytosine:

N6-methyladenine
N4-methylcytosine

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17
Q

What is the role of methylation in bacteria?

A

Protects bacteria’s DNA from cleavage by restriction endonucleases

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18
Q

In E. coli methylation of adenine residues in the sequence ____ is involved in mismatch error correction.

A

GATC

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19
Q

What bases are methylated in eukaryotes?

A

Cytosine only!

5-methylcytosine

20
Q

What is the sequence of methylation in eukaryotes?

A

CG and complementary CG will be also methylated in the corresponding position

21
Q

Is methylation heritable or inheritable?

A

Heritable

22
Q

A ______ promoter tends to be expressed and a _______ promoter tends not to be expressed.

A

unmethylated = expressed

methylated = not expressed

23
Q

How can you reverse the methylation of genes?

A

Treatment with 5-azacytidine, a cytidine analog that cannot be methylated

24
Q

What are common causes of DNA mutation?

A

Mistakes during replication
Deamination of cytosine
UV damage
Chemical damage

25
Q

What happens due to deamination of 5-methylcytosine?

A

CG to AT transition mutation

26
Q

What is a transition point mutation?

A

Exchange of one pyrimidine-purine base pair for another pyrimidine-purine pair.

27
Q

What is a transversion point mutation?

A

Pu-Py exchanged for Py-Pu

This is worse!

28
Q

What are common causes of deletion or insertion mutations?

A

Intercalating agents that fit in between adjacent base pairs

Transposable elements

Triplet repeats

29
Q

What is the worst result of a deletion/insertion mutation?

A

Changing the reading frame

30
Q

What are inter or intra strand break and crosslinks?

A

Photodimerization for example causes intra stand dimerization of adjacent (pyrimidine) dimers.

31
Q

Is O6-alkylguanine an especially deleterious form of DNA damage?

A

Yes

32
Q

What does O6-alkylguanine have a high probability of being base paired with during replication?

A

Thymine

33
Q

How are O6-alkylguanine repaired in prokaryotes and eukaryotes?

A

O6-alkylguanine DNA methyltransferase (MGMT) transfers the methyl group to itself i.e. self alkylates and restores the guanine.

34
Q

How does excision repair work?

A

Damaged DNA is recognized, removed, and then replaced by DNA polymerase

35
Q

What does nucleotide excision repair (NER) fix?

A

Intra strand thymine dimers caused by UV radiation

36
Q

What are the steps of NER?

A
  1. Recognition of damage
  2. Repair proteins stall at damage
  3. Bend DNA
  4. UVrA displaced, UVrC joins complex
  5. Endonuclease cuts 3’ to 5’ and a helicase removes damaged piece
  6. DNA Pol I replaces excised DNA
  7. DNA ligase seals nick.
37
Q

What is base excision repair?

A

DNA-N-glycosylases removed incorrect BASES in DNA

38
Q

What enzyme removed mismatched uracil in prokaryotes?

A

Uracil DNA-N-glycosylase

39
Q

What enzyme repairs DNA in eukaryotes?

A

DNA Pol Beta

40
Q

What two types of mechanisms exist for repairing eukaryotic DNA by excision repair?

A

Short patch BER

Long patch BER

41
Q

What is mismatch repair?

A

Nascent DNA scanned for errors - mismatched bases and single base insertions or deletion

Errors are corrected

42
Q

How does mismatch repair occur?

A

MutHLS system:

  1. Recognition of damage
  2. MutHLS complex searches for methylated GATC sequence closest to damage
  3. MutH (endonuclease) cuts the backbone 5’ to the G in GATC
  4. Helicase unwinds DNA past damage
  5. Exonuclease removes DNA past damage
  6. DNA Pol III fills the gap
  7. Nick in backbone sealed by DNA ligase

It looks for methylated strand because it knows that is the correct parent strand. Daughter strand not yet methylated

43
Q

What genes are affected in patients with CMMRD?

A

MSH (mismatch repair) genes

44
Q

What are common symptoms of CMMRD?

A 
Childhood onset of brain tumors
Colorectal cancers
Neurofibromatosis-1
Cafe au lait spots
Hematological malignancies
45
Q

What are symtpoms of xeroderma pigmentosum?

A

Superficial reddening of the skin
Freckling
Rapid development of skin cancer despite little sun exposure

46
Q

What causes xeroderma pigmentosum?

A

Failure to conduct nucleotide excision repair

47
Q

What are the two types of eukaryotic NER?

A

Global genome NER: probes the genome for lesions

Transcription-coupled NER: removes transcription-blocking lesions to permit unperturbed genome expression

Molecules to Cells (34 decks)

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