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BIOL 200 > PL2 > Flashcards

PL2 Flashcards

1
Q

What is DNA subject to

A

Constant damage

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2
Q

What are mutations

A

Permanent, transmissible changes to the genetic material of a cell

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3
Q

When can mutations occur

A

Spontaneously, by transposable events and by errors during replication

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4
Q

Do mutations transmit to baby in osmotic cells

A

No

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5
Q

What are mutagens

A

Chemical compounds, uv radiation or ionizing radiation that increase the frequency of mutations

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6
Q

What does accumulating damage in somatic cells cause

A

Causes them to lose control over their growth and become cancerous

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7
Q

What are carcinogens and what can they be described as

A

Agents that cause cancer, are often mutagens

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8
Q

What can carcinogens cause

A

Self-sufficiency in growth signals
Insensitivity to antigrowth signals
Evasion of apoptosis
Limitless replicative potential
Tissue invasion and metastasis
Sustained angiogenesis

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9
Q

What are examples of DNA repair

A

Proofreading by DNA polymerase
Base excision repair
Mismatch excision repair
Nucleotide excision repair
Double strand break repair by end joining or by homologous recombination

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10
Q

What kind of activity do polymerases have and what does it affect

A

Proofreading activity that helps increase accuracy

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11
Q

Which polymerases have proofreading or a 3’ to 5’ exonuclease

A

Polymerase epsilon and fancy s but not alpha

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12
Q

What happens with the incorporation of an incorrect base

A

causes polymerase to pause and the 3’ end of the new strand is free to move to the 3’ to 5’ exonuclease site and the mispaired base is removed

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13
Q

What does an exonuclease do

A

Digests nuclear at one end and takes incorrect nucleotide away

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14
Q

What is the most common point mutation

A

C to T

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15
Q

What are the steps that cause mutation in DNA by a single base pair

A

Spontaneous Deamination (c turns to T)
Replication (causes permanent mutation in DNA) that makes two double stranded DNA from a single double stranded DNA

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16
Q

What are the two double stranded DNAs made from replication if mutation isn’t caught

A

Mutant DNA and wild type DNA

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17
Q

Where must repair occur in and what happens once there is repair in base excision repair

A

After deamination but before replication otherwise there will be a permanent mutation in DNA

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18
Q

In a mismatched base pair, which base is correct and which one is wrong

A

T-G mismatches almost always result from deamination of C to U or C to T so T is wrong and should be replaced by C

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19
Q

What are the overall steps of base excision repair (BER)

A
  1. DNA glycosylase breaks the bond between T and the sugar phosphate backbone
  2. APEI endonuclease cuts the DNA strand where it is missing a base
  3. AP lease removes deoxyribose in phosphate leaving a one nucleotide gap
  4. Special DNA polymerase (B) inserts C using G as template, ligand repairs sugar-phosphate backbone
20
Q

What does mismatch excision repair do

A

Fixes errors introduced during replication, including base pair mismatches and insertions or deletions of one or a few nucleotides

21
Q

In mismatch excision repair, which strand is wrong?

A

The newly synthesized strand is wrong

22
Q

When does mismatch excision repair happen

A

After DNA replication

23
Q

How is the newly synthesized strand distinguished in mismatch excision repair

A

3’ end of newly synthesized strand is distinguishable from old strand

24
Q

How does mismatch excision repair work

A

MSH2 and MSH6 recognize the mismatch and distinguished newly synthesized strand

This triggers binding activity of MLH1 endonuclease that cuts newly synthesized strand

DNA helices unwinds and DNA exonuclease digests several nucleotides of daughter strand

DNA polymerase (fancy S) fills in the missing nucleotides using the other strand as template and ligand repairs the sugar-phosphate backbone

25
Q

What does nucleotide excision repair do

A

Fixes DNA regions where chemically modified bases locally distort the double helix

26
Q

What is an example of a nucleotide excision repair problem

A

TT diner caused by radiation where two adjacent T bases become chemically bonded to each other

27
Q

What are other things that can locally distort the double helix

A

Chemicals that can bind to DNA bases including many carcinogens

28
Q

What are the steps of nucleotide excision repair

A

XP-C and 23B protein recognize the distorted double helix

TFIIH, XP-G and RPA unwind helix to make a bubble

XP-F and XP-G cut the damaged strand

DNA polymerase in the missing nucleotides using the other strand as template

Ligament repairs the sugar-phosphate backbone

29
Q

What happens if a TT dimer is not repaired and it enters a replication fork

A
  1. Pol S and POl E stall when they reach a TT dimer
  2. Translesion Pol n can read through the TT dimer but it lacks proofreading activity
  3. Region in the vicinity of the TT dimer will likely contain mutations caused by replication errors
    4.Pol n gets replace by normal DNA polymerases
30
Q

What can cause double strand beaks in DNA and why

A

Radiation and some anti cancer drugs because they prevent growth of cancer cells

31
Q

What happens if a double strand break is not repaired

A

Then the part of the chromosome distal to the break would be lost at the next cell division likely causing lethality

32
Q

What rejoins the broken chromosome ends of a double strand break repair end joining but what ends up happening

A

NHEJ but base pairs are usually lost at joining point producing a small deletion

33
Q

What are the steps of double strand break repair end joining

A
  1. Ku and DNA-pk bind the end of a double strand break
  2. When two DSBs bound by there proteins come together; they recruit nucleuses that remove several bases
  3. The two double stranded molecules are then lighted together
34
Q

How can this mechanism produce chromosomal rearrangements

A

It does not ensure that what is lighted together originated from adjacent parts of the same chromosome so it can fuse DSBs originating from different chromosomes or far apart on the same one

35
Q

What happens if possible deletion is made in coding region of that gene

A

Function of the gene will be wiped out

36
Q

What is the damaged DNA sequence replaced with in double strand break repair by homologous recombination and what does it involve

A

A copy of an undamaged copy of the same sequence on the homologous chromosome in diploid organisms

Involves exchange of strand between separate DNA molecules (recombination)

37
Q

What is recombination in double strand break repair by homologous recombination

A

Exchange of strands between separate DNA molecules

38
Q

What are the BRCA 1 and 2 genes in DSBRBHR and what do they do

A

Mutations associated with increased susceptibility to breast cancer

Encode proteins involved in homologous recombination repair

39
Q

What is something that can be repaired by DSBRBHR

A

A collapsed replication fork

40
Q

Why is it bad that synthesis of daughter strand stops when there is a break in one of the parent strands

A

Dangerous to daughter cell because of partial chromosome loss

41
Q

What happens after replication fork collapse in DSBRBHR

A

Daughter strand gets lighted to segment of parental strand to make an unbroken chromosome

42
Q

Why is strand invasion a key part of recombination process in DSBRBHR

A

The newly ligated strand anneals to the other daughter strand whose synthesis was interrupted by the break

43
Q

What happens after strand invasion in DSBRBHR

A

Branch migration: increased stretch of daughter strand denatures from broken parent strand and anneals to other daughter strand

which allows broken parent strand to cross over and anneal to other parental strand

44
Q

What does the diagonal represent in the crossing of parent and daughter strand in branch migration

A

A single phosphodiester bond between adjacent nucleotides

45
Q

What happens after branch migration

A

Lighting ends produces a structure similar to replication fork

Recruitment of replication fork allows for replication to continue

46
Q

Why does Pol A not have any proofreading activity

A

It doesn’t make any bases and its work gets replaced by Pol S

BIOL 200 (13 decks)

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