Chromosome Structure Flashcards

1
Q

At what stage of the cell cycle can chromosomes easily be distinguished?

A

During metaphase during mitosis.

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2
Q

In mammals their SEX chromosomes pose an inherent imbalance in gene expression between sexes

Why is this? And how is this overcome?

A

Because in males their Y chromosomes are shorter than the X chromosomes

Thus there are more genes on the X chromosome

So random inactivation of one of the X chromosomes restores the balance

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3
Q

Note chromsomes arent all the same size

In interphase chomosomes are easily identifiable

What do they look like under the electron microscope?

A

Under the electron microscope these interphase chromatin resemble beads. These beads show nucleosides.

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4
Q

In interphase what is the structure of chromatin fibres?

A

These are tightly coiled

They are around 30nm

These chromatin can be further condensed of opened up for repair and transcription

These structures are said to be supercoiled

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5
Q

What are nucleosomes?

A

These are histones with DNA coiled around them.

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6
Q

How many different types of histones are there? What do these make? What does DNA coil around?

A

There are 4 types of histone

H2a h2b h3 and h4. There are 2 sets of these

These make up a histoctomer

Note its the DNA which coils around this histoctomer complex

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7
Q

What property of histoctomer complexes help DNA to bind?

A

They are positively charged. This allows for electrostatic interactions with the phosphate backbone of the DNA strand and the octomer itself.

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8
Q

Where do each of the histoctomers histones N terminus tails project? What do these projects allow for?

A

The N terminus tails project into outer space.

These projections allow DNA repair machinery to bind to the DNA

These N terminus tails are free to bind to interact with other proteins facilitating regulation of chromatin structure and function.

These projections can change the shape of histones.

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9
Q

What is important to note about the histoctomer core? And what does this mean?

A

Attraction to the histoctomer core by DNA is relatively weak

This means that it can be moved around DNA with the help of enzymes.

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10
Q

So note, histoctomers can move up and down the DNA strand via enzymes, what does this mean?

A

This means one region of the DNA strand may have more histoctomers and one region may have less.

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11
Q

What is the role of the histone one linker histone?

A

This associates with DNA

Its role is to clip incoming DNA and outgoing DNA at the entry and exit points of the nucelosome.

  • this means the histoctomer cannot move backwards and forwards along the DNA sequence
  • its clipped to one position
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12
Q

What is typical for DNA such as heterochromatin which have a high number of histone one?

A

These heterochromatin are relatively stable

This means it is hard to access their DNA. This is because when associated with the histone 1 the DNA is tightly coiled and thus not accessible

These DNA strands are also very condensed and transcriptionally inert

These chromatin are also silent! So they are not transcribed.

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13
Q

Regions of DNA can be is histone depleted, what does this mean and what does this allow?

A

Regions of DNA that are histone depleted just means there are no histones in these places.
(Due to the nature of the histoctomers moving along the DNA strands - this isnt in reference to the histone 1 linker histones)

This allows the DNA strand to be accessible to other types of interacting DNA proteins which have the ability to recognise specific DNA points.

These other proteins may help DNA polymerase to bind

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14
Q

Remember in this lecture when we talk about DNA strands this is in reference to DNA in the nucleus

Think of chromosomes within the nucleus as free floating and thus they can form bundles. They dont have the DNA rep structure, instead they are linear

What is the structure of interphase chromatin? What are their sub territories called? What can these sub territories do?

A

Interphase chromatin are arranged into different territories within territories (like a russian doll model) (remember in the NUCLEUS chromsomes are NOT condensed. Their DNA is linear and free floating)

These sub territories are referred to as fractal globules

These sub territories or fractal globular domains which make up the DNA

These globular fractions can condense of decondense without becoming knotted

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15
Q

What is important to note about chromosome structure within the nucleus?

A

Think of chromosomes within the nucleus as free floating and thus they can form bundles. They dont have the DNA rep structure, instead they are linear

Thus they can form the globular structures.

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16
Q

How is DNA arranged in the nucleus of a cell? And what gives them this arrangement?

This is in reference to inner and outer domains

A

Inactive DNA such as heterochromatin form a ring around the outskirts of the nucleus

(This is called the periphery of the nucleus or the outer domain)

The inner region of the nucleus is where you find RNA transcripts. Here chromatin can be transcribed

(This is the inner domain of the nucleus)

This arrangement is made by enzymes

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17
Q

What is important to note about genes within the nucleus of the cell?

A

They can be inactive or active

Dont assume all are active!

And remember the inactive genes are at the periphery of the nucleus

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18
Q

What happens to genes which were inactive when they become inactive? And how can we see this?

This refers to genes in the nucleus.

A

When the nucleus receives a signal from a growth factor, inactive genes found on the DNA at the periphery move further into the nucleus

When the particular gene becomes active, it tugs the rest of the inactive chromosomes towards the centre of the nucleus

This is where the enzymes are for transcription

We can see this gene movement with fluorescent tagging

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19
Q

What are the features of eukaryotic chromosomes that allow them to function?

A

Eukaryotic chromosomes are linear - they aren’t condensed like chromosomes in replicating DNA and they can for globules.

They have defined ends called telomeres (remember these aren’t enzymes. Telomerase is the enzyme)

The chromosomes have different sites where DNA replication can be initiated from

20
Q

What is a centromere? And what are kinetochores?

A

Centromeres are repeated DNA sequences that mitotic spindles can bind to. This ensures sister chromatids can separate

Kinetochores are protein complexes that bind mitotic spindles to the centromere

21
Q

What do chromosomes allow for?

A

Reliable and complete DNA replication

Segregation of duplicated chromosomes during cell division.

22
Q

So what is the definition of a telomere and definition of a DNA origin?

A

Telomeres are DNA sequences at the end of LINEAR chromsomes (within the DNA) these maintain chromosomal integrity

DNA origin is parts of the DNA sequence where RNA replication is initiated

23
Q

What is the typical telomeric repeated pattern?

A

These are a series of repeats at the end of the DNA strand. These are made by telomerase which is a DNA polymerase.

The repeat is TTAGGG

The telomere stops the chance of DNA loss after replication. This stops the DNA shortening.

24
Q

What does the telomere repeat create?

A

It creates a overhang. This is single stranded.

Thus the telomere ends of chromosomes isnt fully double stranded as there is still the telomere overhang of one of the strands which ISNT cut off.

25
Q

What are centromeres made up of? And what is the function of this structure?

A

The centromere is made up of monomeric repeats

There are between 150 to 200 base pairs in the centromere repeat

This repeat allows for the recruitment of histoctomers which allows the kinetochore to bind and connect the mitotic spindles to the DNA itself.

26
Q

The structure of the kinetochore?

And remember this connects spindle fibres to the centromere

A

The kinetochore has a inner and outer plate

The spindles microtubules project into the outer plate of the kinetochore

This is stuck onto the inner kinetochore plate

This inner plate is attached to the centromere (which is a series of repeats remember)

27
Q

What is the centromeric DNA made up of? As in order repeats? What histones do these specific order repeats bind to? (Remember the centromere also bind to histoctomeres)

A

Its made up of higher and lower order repeats

Some of the lower order repeats inside of the higher order repeats bind to a specific histone 3 variant called CPA centromeric protein A

These higher order repeats can create nucleosomes that are rich in CPA

This CPA makes alot of contacts with the inner kinetochore plate and the centromere

So this CPA is BETWEEN the inner kinetochore plate and the centromeric repeats

28
Q

The outer and inner kinetochore structures?

A

Outer is like a cylinder that has a ring which allows microtubules to fit into it

Inner has a funnel shape

29
Q

Yeast as models for the centromeres and kinetochore plates:

What is the key structure?

How does the inner kinetochore plate bind to the outer kinetochore plate in yeast

A

Yeast have one centromere which is made up of one nucleosome, which has a single CPA and a histoctomer

the inner kinetochore plate binds to the outer kinetochore plate in yeast via attach to helical proteins

Remember like in humans the outer kinetochore plate is a cylinder which allows microtubules to insert in and the inner plate is a funnel

30
Q

The protein coding parts of the eukaryotic genome of DNA only make up 1.5% of the DNA strand?

What makes up the rest?

A

50% of the DNA is made of repeated DNA sequence elements (these can be transposons)

30% is non repetitive unique sequence DNA (these are regulatory elements)

About 18.5% of the DNA is made of introns.

31
Q

What is important to note as the number of genes in a organism increases?

A

So does the amount of non coding DNA in the genome.

The non repetitive DNA (30% of the DNA)is made or transcriptional and regulatory elements which recruit specific binding proteins.

These sequences can allow DNA polymerase to bind to synthesise the DNA strand and can allow RNA polymerase to transcribe proteins from the DNA strand.

32
Q

What are transposons? How many types are there? What is notable about transposons?

A

Note these make up the DNA repeated sequence elements

There are three types

  • DNA transposons
  • retroviral transposons
  • non retroviral transposons

Transposons are mobile elements thus they can move around the DNA strand / genome

33
Q

How much of the DNA do DNA transposons make up? How do they move around and by which enzyme?

A

DNA transposons make up about 5% of the human genome

They move around the DNA strand via a cut and paste method by the enzyme transposase

The DNA transposase cuts the DNA transposon out of sequence where they are found. This sequence is the repaired and the transposon is reinserted somewhere out in the DNA

34
Q

What is the negatives and positives of DNA transposons?

A

Because they move around the DNA genome they can disrupt gene expression and genome integrity

This movement however an allow for genomic evolution.

35
Q

What are the transposon elements which allow for cut and paste enzymes to cut out DNA transposons

A

P element in drosophila

Tn3/ Tn10 in E coli

The activator dissociator in miaze

36
Q

What is the example of Maize seeds and DNA transposons?

A

DNA transposons are powerful mutagens in maize

They can cause the pigment in miaze to change from normal

This is because one transposons can jump from one gene to another gene remember and as it does this is mutates. The colour coding enzyme thus changes due to this movement.
(The transposon rearranges the gene order)

37
Q

8% of the genome is retroviral transposons.

What are these? What do these transposons create?

A

These are transposons which are made by virus and inserted into human DNA

These transposons are the transcribed to produce RNA copies of the genome.

These RNA copies then make viral capsid proteins and envelope proteins which make up viral particles. These contain a RNA copy of the genome and a retroviral protein known as reverse trancriptase

38
Q

What does reverse transcriptase do?

A

This copys and duplicates the retroviral genomes (remember these had already been copied from the transposons)

These RNA copies are converted to DNA. And the viral genome intergrase may put these DNA copies elsewhere in the genome

39
Q

What can retroviral elements made by retroviral transposons do? And can retroviral transposons escaped the cell?

A

Retroviral elements of the DNA strand produce viral particles. These can escape and effect other cells

However retroviral transposons - never escape the cell. As they reintegrate into the cell without making viral particles

40
Q

What is important to note about the more complex organisms?

A

They have huge numbers of repeated DNA sequences

41
Q

What is the features common to DNA transposons, retroviral transposons and ploy A transposons?

A

They are all mobile genetic transposable elements

Together they make up about half of the genome

42
Q

What are polyA retrotransposons?

A

These are abundant in vertebrate genomes and replicate via RNA intermediate (like retroviral transposons do)

These also encode for a reverse transcriptase (like the other transposon) and this makes RNA transcript copies

This then makes a DNA copy.

43
Q

What is the stages of duplication by reverse transcriptases which is made by the polyA retrotransposon?

A

The RNA transcriptase needs to capture a copy of the RNA transcript made by the PolyA retrotransposon

It must then make the copy

Note once the reverse transcriptase has made the DNA copy from the RNA it is reinserted back into the original DNA of the cell

The intergrase enzyme cleaves the DNA target on both strands.

Then inserts the poly A retrotraposon

This can affect the properties of the cell in good and bad way?

44
Q

What causes haemophilia ?

A

A polyA retrotransposon L1 had been randomly insert into the protein coding sequence of a clotting factor

This causes the clotting agent not to work

Remember transposon insert into random locations and thus their effect on the genome can be good or bad.

45
Q

What is important about most transposon elements?

A

They are defective so thus they dont work.

Like the ALu genes which are transposons.

There are half mill genes similar to this in mice