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MCB 2020 > 2.2 DNA Replication and Repair > Flashcards

2.2 DNA Replication and Repair Flashcards

1
Q

What are chromosomes made of?

A
  • Chromatin which is one third DNA and two thirds protein.
  • Beads on a string, with bead being nucleosomes.
  • They represent DNA wrapped around an octamer of Histone proteins
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2
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3
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4
Q

What force helps the DNA and histones bind tightly?

A
  • DNA is negative charged due to phosphate groups
  • Histones are positively charged (>20% lysine and arginines)
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5
Q

What are the two forms of chromatin?

A
  • Euchromatin is open and accessible to other molecules (for transcription)
  • Heterochromatin is highly compacted and generally not transcribed. Found in regions of the chromosomes like centromeres and telomeres where there are few genes
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6
Q

What four modifications can happen to the histone tails?

A
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7
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8
Q

What are the three significant parts of a mitotic chromosome structure?

A
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9
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10
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11
Q

What is the origin of replication? And two features

A
  • A location on the chromosome where DNA replication is initiated. Eukaryotes have multiple origins of replication on each linear chromosome
  • Features - AT rich so it’s easier to separate the two DNA strands, easier as AT is 2 hydrogen bonds whereas GC is three
  • enriched for H4K20me2 (binding site for ORC), a histone modification that identified origin of replication
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12
Q

What is the process of DNA replication initiation in eukaryotes?

A
  1. The ORC (origin recognition complex) binds to the origin.
  2. A DNA helicase then binds, to complete the prereplicative complex….then S phase begin
  3. S-Cdk phosphorylates many targets assocaited with DNA synthesis, such as the helicase and ORC
  4. Helicase melts the AT rich area, DnA polymerase is loaded and the two replication forks head off in opposite directions
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13
Q

What is the problem with DNA replication?

A
  • The leading strand is fully replicated
  • But on the lagging strand the last part of the chromosome (where the final RNA-primer was placed) cannot be replicated with DNA
  • Exonucleases will remove the single stranded overhang
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14
Q

How does the problem with DNA replication affect the length of the chromosomes?

A
  • Each cell cyle will shorten the chromsome by 50-100bp
  • This is a normal process in somatic cells of the body which will typically only divide 50-70 times before senescing (ceasing division)
  • This process is opposed by telomerase and telomeres
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15
Q

What are telomeres?

A

A protective stucture at both ends of a linear chromosome, consisting of a tandem repeat of the sequence GGGTTA, and associated proteins, which serves to maintain the integrity of chromosomes.

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16
Q

What is telomerase?

A

A ribonucleoprotein (protein and RNA) that elongates telomere sequences.

17
Q

What are the two key aspects of telomerase?

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18
Q

What is the process of telomere extension by telomerase?

A
19
Q

How does telomerase relate to ageing?

A
  • Loss of telomeres causes cellular senescence
  • Telomere length correlates with age
20
Q

What is Werner syndrome?

A
21
Q

What is the centromere?

A

The heterochromatic region of a chromosome which joins sister chromatids during mitosis. It is the region to which microtubules attach via the kinetochore

22
Q

What are two key components of the centromere?

A
23
Q

Where do microtubules bind to the centromere?

A
  • To the kinetochore
  • VIa a specific modification of H3 Lysine 4 that is methylated
24
Q

What are some examples of chromosomal aberrations?

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25
Q

What are examples of centromere issues giving rise to chromosomal aberrations?

A
26
Q

What is Down Syndrome?

A
  • Causes physical growth delays, characteristic facial features, mild/moderate intellectual disability
  • Cuased by a 3rd copy of chromosome 21
  • Most cases are due to meiotic non-disjunction
  • 2-3% due to Robertsonian Translocation
27
Q

What is an acrocentric chromosome?

A

A chromosome in which the centromere is located close to the end of the chromosome

28
Q

What is a Robertsonian translocation?

A

Two chromosomes joining at the centromere region

29
Q

How does a Robertsonian translocation bring about Down syndrome?

A

Fusion in the centromere between 14 and 21 and the small clump is lost

30
Q

What is contained in the short arms of the acrocentric chromosomes that is lost due to Robertsonian translocation?

A
  • The short (p) arms of the acrocentric chromosomes 13, 14, 15, 21 and 22 do not contain essential genes but contain tRNA and rRNA loci which are present in multiple copies.
  • If you lose those parts they will still be elsewhere in the genome
31
Q

What is the pattern of inheritance that leads to trisomy from Robertsonian translocations?

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32
Q

What are the mutagens?

A

Viruses, chemicals, reactive oxygen speices

33
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36
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37
Q

What happens in depurination?

A

Purines are G and A bases. Depurination is a hydrolytic attack on the bond so we lose the purine

38
Q

What can depurination cause?

A
39
Q

What can deamination of C cause?

A

MCB 2020 (38 decks)

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