MCB Lecture 19 Cell Cycle, Centromeres, DNA Damage and repair Flashcards

0
Q

Describe the overall chromosome structure throughout interphase and mitosis

A

During interphase, the chromosome is compacted to a much lesser extent

During mitosis it is very compacted

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1
Q

What are the phases of the cell cycle?

A

G1
S
G2
M

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2
Q

What are the structural requirements of a chromosome?

A

2 telomeres
1 centromere
Many origins of replication

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3
Q

What can abnormalities in centromere number lead to? Give two examples

A

Problems with chromosome segregation

No centromeres: the chromosomes will segregate randomly
Two centromeres: two spindles will attach from each pole
The chromosome will break because it is being pulled by two different spindles

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4
Q

What type of DNA are centromeres made up of?

A

The centric region has a H3 histone variant

The peri centric region is heterochromatin: ie very dense

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5
Q

How many repeats of satellite DNA are there in general in a centromere?

A

1500-3000

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6
Q

Compare human centromeres with those in other organisms

A

Those in humans are much longer regions of DNA and have many repeats

Simpler organisms have more unique sequences but they are shorter

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7
Q

Describe the chromatin in centromeres. How does it differ from normal chromatin?

A

The chromatin in centromeres has a H3 variant
CENP-A

As well as
H3K9me2 in the peri centric chromosome

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8
Q

Why does centromere chromatin differ? What is its function?

A

The CENP-A variant binds to the kinetochore protein that must associate with centromeres.

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9
Q

What is special about the peri centric chromatin in centromeres?

A

It is very dense; dimethylated

Conventional heterochromatin modifications: H3K9me3

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10
Q

What happens if a centromeres function is lost?

A

A neocentromere can form from a previously inactive centromere

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11
Q

What are the requirements for a centromere in terms of definition?

A

It must have mitotic spindle attachments

Alpha-satellites are not vital for the attachment of spindle, so it is thus not in the definition

  • heterochromatin
  • H3K4me2 (centric, non kinetochore binding)
  • CENP-A
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12
Q

What is a robertsonian translocation?

What sort of chromosomes does this occur in?

A

This is when two different chromosomes break at the centromere and reattach to the wrong one

Acrocentric chromosomes

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13
Q

What can happen to the centromere in a robertsonian translocation? (3)

A

Fusion
One lost: only one chromosome
Inactivation of one of them

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14
Q

What is normally on the p arm of the chromosomes that undergo Robertsonian Translocation?

A

rRNA and tRNA information that is present elsewhere in the genome. Thus it is not so dire if this is lost

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15
Q

What disorders can arise from Robertsonian Translocations?

Describe how this may occur

A

Trisomy 21

One of the parents has a Robertsonian translocation between cr. 21 and another Afrocentric chromosome

When this individual produces gametes, there is the possibility of having two copies of the q arm of chromosome 21 because it is fused onto the q arm of the other chromosome

In fertilisation, the individual will now have three copies, because another is received from the other parent

16
Q

What is a replication origin?

A

This is the region where DNA replication starts

17
Q

How many replication origins does a eukaryotic cell have?

A

Many

18
Q

Origins of replication are … rich

A

AT

19
Q

Describe the process of initiation of replication

A
  1. ORC protein complex binds to the AT region
  2. Cdc6 and Cdt1 associate
  3. Mcm associates
    We now have the prereplicative complex
  4. Cdk phosphorylates cdc6, and it dissociates, also cdt1
  5. The helix unzips and is replicated
20
Q

Describe the process of elongation of DNA Replication

Name all the enzymes

A
Helicase
Primase
DNApol III
RNA pimer
Topoisomerase
ssBP
Ligase connects Okazaki fragments
DNA pol I
21
Q

What is a telomere?

A

It is a repetitive region on the end of chromosomes

It prevents degradation of the chromosome during DNA replication

22
Q

What is the structure of telomerase?

How does this relate to function?

A

RNA part and protein part -> ribonucleoprotein

The RNA section provides a template for telomere synthesis

The protein part reverse transcribes DNA from the RNA template in the telomerase
TERT

23
Q

What is the repeating DNA sequence in telomeres?

A

TTAGGG

24
Q

Which cells have high telomerase activity?

A

Cancer cells
Stem cells
Germ line cells

25
Q

List a few ways that DNA damage can occur

A
Chemical mutagens
Viruses, infection
UV
Radiation
Pollution and toxins
26
Q

What are thymine dimers?

A

When two thymine nucleotides next to each other bond in a different way, causing a kink in the DNA strand

27
Q

What is deamination?

A

This is when a Cytosine is converted to a uracil

28
Q

Which type of repair can fix thymine dimers? Give a basic outline of the process

A

Nucleotide excision repair

29
Q

Which type of repair can fix depurination?

A

Base excision repair

30
Q

Which type of repair can fix deamination?

A

Base excision repair

31
Q

Which type of repair can fix double stranded breaks?

A

Double stranded break repair

32
Q

What is depurination?

A

The A or G is removed

33
Q

Give an example of a chromatin remodelling complex

A

SWI/SNF

34
Q

What is the function of SWI/SNF?

A

This is a chromatin remodelling complex; it gives greater access to the DNA to the RNA pol

35
Q

What is the name of the complex at the start of DNA replication?

A

The pre-replicative complex

36
Q

WHat type of repair is required for DNA replication error?

A

Mismatch repair

37
Q

Which type of repair is required for a methylated nucleotide?

A

Base excision repair