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BLGY1115 > Chromatin and Genomes > Flashcards

Chromatin and Genomes Flashcards

1
Q

Problems With Having a Large Genome

A

-have to compromise between saving space and storing DNA and keeping it selectively available for use

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2
Q

DNA Structure Through Cell Phases

A
  • DNA structure is dynamic
  • accessibility of DNA varies through cell phases
  • Metaphase Chromosomes have maximum condensation of DNA to facilitate amplification
  • Interphase nucleus has the most spread out and accessible DNA for transcription
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3
Q

Chromatin

A
  • DNA and protein complexes

- allows genetic information to be stored and read

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4
Q

Euchromatin

A

genetic region containing genes that are used ( e.g. for transcription), a region that is opened up extensively

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5
Q

Heterochromatin

A

-genetic region containing genes that appear not to be use, highly condensed

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6
Q

What direction is DNA read in?

A

5’ to 3’ on the top strand

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7
Q

Pyrimadines

A

cytosine
thyamine
uracil

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8
Q

Purines

A

andenine

guanine

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9
Q

Nucleotide

A

pentose sugar
nitrogenous base
phosphate group

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10
Q

Beads on a String

A
  • After initial unpacking (dissolving in various ions)
  • DNA appears as a strand with beads on it
  • The ‘beads’ are nucleosomes
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11
Q

Nucleosomes

A
  • 2 loops of DNA wrapped around 8 histone molecules
  • the octameric histone core is made up of 2xH2A, 2xH2B, 2xH3 and 2xH4
  • H3 and H4 form heterodimers
  • H2A and H2B form heterodimers
  • histone protein tails stick out from the nucleosome complex allowing it to interact with the outside
  • enzymes can interact with and modify the tails and other enzymes can detect these signals
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12
Q

Condensed Chromatin Solenoid

A

-6 nucleosomes held together in a circle by six histone 1 molecules, one inbetween each pair of nucleosomes

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13
Q

Protein Scaffold

A
  • protein complexes on the inner side of the nuclear membrane
  • attach to certain regions of chromatin
  • forming a 3D network
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14
Q

Levels of Chromatin Packing

A
  • DNA double helix (2nm)
  • nucleosomes (10nm)
  • soleoids (30nm)
  • attachment to protein scaffold and folding of the chain (loops 300nm long)
  • metaphase chromosome (1400nm)
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15
Q

Organisation and Territories

A
  • interphase chromosomes have preferred positions in the nucleus
  • genes have specific positions within interphase chromosomes called territories
  • there is very limited intermingling of chromatin between chromosome territories
  • if a gene is moved to a different chromosome it is often found that it doesn’t work
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16
Q

Gene -> Phenotype

A
  • chromatin
  • DNA unpacking involving DNA demethylation and histone acetylation
  • DNA
  • transcription
  • RNA with introns
  • RNA processing
  • mRNA
  • transport out of nucleus
  • translation
  • polypeptide
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17
Q

Which genes are found in condensed chromatin?

A

inactive genes

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18
Q

Which genes are found in open chromatin?

A

active genes

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19
Q

Opportunities for Gene Regulation

A
  • local changes in accessibility of genes prevent certain proteins from being transcribed in certain cells
  • chromosome packing correlates with gene expression
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20
Q

What do genes do?

A
  • genes don’t just code for proteins
  • only ~1% of the human genome codes for proteins
  • the other 99% is pseudogenes, non-functional copies of genes
  • these regions are created when genes are transcribed to RNA but the RNA is then reverse transcribed to cDNA which is integrated into the genome
  • at least 75% of the genome is transcribed but much of the function of these RNAs is unknown
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21
Q

What are the two types of repetitive sequences?

A
  • tandem repetitive sequences

- dispersed repetitive sequences

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22
Q

Cell Response to Repetitiveness in the Genome

A
  • cells can sense repetitiveness

- repetitive regions are often condensed to prevent expression

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23
Q

Tandem Repetitive Sequences

A
  • repeats aligned at one locus

- e.g. telomeres, centromeres

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24
Q

Dispersed Repetitive Sequences

A
  • regions that are repeated but the repeats are spread throughout the genome
  • e.g. transposons, retrotransposons
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25
Q

Transposable Elements

A
  • DNA elements that can migrate or amplify

- usually controlled by chromatin condensation

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26
Q

Retrotransposable Elements

A
  • DNA elements that can migrate or amplify via RNA

- usually controlled by chromatin condensation

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27
Q

Transposons

A
  • a transposon is a sequence of DNA that has repeats at the start and end of the sequence
  • the repeats at the start and end may be inverted
  • a transposon is able to migrate from its existing site to a target site
  • transposons accumulate in the genome over the organisms lifetime
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28
Q

Retrotransposons

A
  • the same as a transposon but migrates using RNA
  • retrotransposon is transcribed to RNA
  • RNA is reverse transcribed to cDNA
  • this cDNA copy is inserted at a target site elsewhere in the genome
  • we accumulate more retrotransposons than transposons as retrotransposons replicate each time they migrate
  • a retrovirus that has lost its gag and env regions
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29
Q

Long Terminal Repeat

A
  • LTR

- signals for genome to try and inactivate retroviruses when they integrate into the genome

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30
Q

Retrovirus

A
  • sequence of DNA inserted into our genome by a virus
  • consists of a long tandem repeat at each end, and three coding regions, gag, pol and env
  • gag codes for 2 capsid proteins
  • pol encodes a multi function protein with reverse transcriptase function, proteinase and integrase activity
  • env encodes envelope proteins that allow the virus to interact with host cells
31
Q

Retroposon

A
  • retrovirus that has lost its long terminal repeats and only has short ones
  • SINEs (short interspersed elements) are retroposons without reverse transcriptase, ~100-400bp
  • LINEs (long interspersed elements) are retroposons that have reverse transcriptase, ~6kbp
32
Q

DNA Replication

A
  • many origins of replication long the DNA strand where polymerase can start synthesis of a second strand
  • all of these regions are joined up until only the ends of the strands are left
  • on the top strand (5’ to 3’) the polymerase can just continue until it falls off
  • but on the bottom strand the polymerse has to start at the end of the strand as it can only go 5’ to 3’
  • the polymerase has to have a primer it sits on before beginning replication so there is always a region right at the end of the strand that it cant synthesise
  • telomerase carries a dhort RNA primer which it uses as a template to synthesise cDNA using reverse transcriptase
  • this cDNA sequence is attached to the end of the chromosome one nucleotide at a time
33
Q

Telomeres

A
  • more than 1000 tandem repeats of the same short sequence (TTAGGG in humans) at the end of every chromosome
  • there is a special enzyme, telomerase that can maintain and replicate these ends
  • telomerase is functional in embryonic stem cells and cancer cells but not in most somatic cells
  • this means that telomeres (and also chromosomes) shrink with every replication
34
Q

Centromere

A
  • part of the chromosome to which the spindle attaches
  • highly condensed sequence
  • centromeres don’t share a common sequence, the only requirement is that the sequence is highly repetitive
  • 240kbp - several Mbp long
  • each chromosome has 1 centromere
35
Q

Making a Centromere

A
  • the centromere is just the most condensed region on a chromosome, wherever that happens to be
  • by removing some repeats from the current centromere and moving them elsewhere to make another region the most repetitive, it is possible to move the centromere
36
Q

Interphase

A
  • Growth 1
  • Synthesis
  • Growth 2
37
Q

Miotic Phase

A

Mitosis

Cytokinesis

38
Q

Chromosome Duplication

A

-produces two sister chromatids joined together at their centromeres

39
Q

Mitosis

Stages

A
  • Prophase
  • Prometaphase
  • Metaphase
  • Anaphase
  • Telophase
40
Q

Mitosis

Prophase

A
  • chromatin condenses

- spindle forms

41
Q

Mitosis

Prometaphase

A
  • spindle poles reach fixed positions

- nuclear envelope breaks down

42
Q

Mitosis

Metaphase

A

-alignment of sister chromatids on the metaphase plate

43
Q

Mitosis

Anaphase

A

-separation of sister chromatids by spindle

44
Q

Mitosis

Telophase

A
  • one copy of each chromatid at each pole

- reformation of the nuclear envelope

45
Q

Nuclear Envelope During Mitosis

A
  • in metaphase phosphorylation of lamins occurs leading to the break down of the nuclear envelope
  • in anaphase dephosphorylation of the lamins occurs leading to reformation of the scaffold
  • in early telophase fragments of the nuclear envelope start collecting around the DNA
  • in late telophase the fragments fuse reforming the nuclear envelope
46
Q

Lamins

A
  • major architectural proteins lining the inside of the nuclear membrane
  • provides mechanical stability and platform for binding of proteins and chromatin
47
Q

Cell Division

Plants vs Animals

A
  • animals - cleavage furrow

- plants - cell plate formation

48
Q

Bacterial DNA Replication

A
  • only one chromosome, a single loop of DNA
  • one origin of replication
  • bacterial binary fission
49
Q

Nucleoid

A

the place in a bacterial cell where the DNA is held

50
Q

Control of Cell Division

Contact Inhibition

A
  • cells divide until they come into contact with another cell
  • then division stops
51
Q

Contact Inhibition

Healthy Cells vs Cancer Cells

A
  • when normal cells are grown in a petri dish, they grow until a monolayer is formed
  • a one cell thick layer across the bottom of the dish
  • when cancer cells are grown in the petri dish, they keep growing forming many layers
52
Q

Cancer

A
  • uncontrolled growth of cells normally regulated

- loss of cell cycle control

53
Q

Susceptibility to Cancer

A
  • one defective copy of an autosomal gene does not normally have consequences as there is a normal copy on the other chromosome
  • but if the normal gene is lost or inactivated then the only source of information is the mutant
  • mutations that increase susceptibility to cancer are acquired considerably after fertilisation i.e. in somatic cells
  • low frequency, 1 in 10^8
54
Q

BRCA1 and Breast Cancer

A
  • on mutant allele gives a 60% chance of breast cancer by the age of 50
  • normal alleles give a 2% chance of breast cancer by the age of 50
  • BRAC1 is probably involved in DNA repair
55
Q

Purpose of Recombination

A
  • increased genetic diversity
  • repair damage
  • control gene expression
56
Q

Recombination and Crossing Over

A
  • in prophase sister chromatids cross over at points called chiasmata
  • they exchange genetic information
57
Q

Mutation

Definition

A

-permanent change in a gene

58
Q

What are the types of mutation?

A
  • point mutations

- insertions / deletions

59
Q

Common Mutagens

A
  • free radicals in oxygen
  • cigarette smoke
  • 5-fluororaol
  • x rays
  • UV rays
  • cisplatin
60
Q

Repair of Errors

A
  • proof reading by exonucleases during replication
  • reversal of damage
  • repair of damage
61
Q

Sickle Cell Anaemia

A
  • caused by a single mutation
  • an individual with two sickled copies is unlikely to survive
  • but a carrier is more likely to survive malaria
  • so the sickle allele persists
62
Q

Sexual Life Cycle

A

alternation of haploid and diploid stages

63
Q

At what life cycle stage do higher eukaryotes replicate by mitosis?

A

diploid stages

64
Q

When in their life cycle are animals haploid?

A

only during sexual stages

65
Q

Lower Eukaryote Life Cycles and Replication

A
  • some lower eukaryotes only multiply during haploid stages of life cycle
  • spend much of life cycle as haploid
  • e.g. most fungi, some algae, protozoa
66
Q

When in their life cycle do plants replicate?

A

during both haploid and diploid stages

67
Q

Bacteria Asexual Reproduction

A
  • very rapid
  • clonal
  • not good for diversity
68
Q

Benefits of Sexual Reprouction

A
  • competitive advantage in an unpredictable environment
  • if parent produces many offspring with a wide variety of gene combinations then there is a better chance that at least one of the offspring having the assortment of features necessary for survival
  • spread and sharing of beneficial mutations is possible
69
Q

Meiosis 1

Purpose

A

-reduces diploid cell to two haploid cells with duplicated chromosomes

70
Q

Synapsis

A

pairing of two homologous chromosomes

71
Q

What are the two types of cell death?

A
  • Necrosis

- apoptosis / programed cell death

72
Q

Necrosis

A

-premature death of cells due to injury, toxins, inflammation or infection with cell lysis and release of intracellular content

73
Q

Apoptosis

A
  • aka programed cell death
  • suicide activation
  • DNA fragmentation
  • cytoplasm shrinkage
  • membrane changes without lysis or damage to neighbouring cells

BLGY1115 (10 decks)

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