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Cell Biology > Chromosomes > Flashcards

Chromosomes Flashcards

1
Q

What is each chromosome made of?

A

1 linear strand of DNA

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2
Q

When is DNA most tightly packed?

A

When cells are dividing

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3
Q

What is a karyotype?

A

No., size & shape of chromosomes in the nucleus

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4
Q

What is different about the chromosomes in Klinefelter’s syndrome?

A

XXY

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5
Q

What is a nucleosome?

How many times is the DNA wound per histone?

How many base pairs are wrapped around a histone?

A

Length of DNA coiled around a core of histones

1.67

147

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6
Q

What are the 4 core histones?

What do 2 pairs of tetramers form when bound together?

A

H2A
H2B
H3
H4

An octamer

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7
Q

What is a nucleosome made up of?

A

2 core histones
Linker DNA
H1 (a histone)

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8
Q

How are nucleosomes dynamic?

A
  1. Chromatin remodelling factors slide along DNA
  2. Exchange histone octamers or subunits
  3. Remove core histones
    - -> alters structure
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9
Q

What is special about the histone tails that stick out?

A

They can be modified by chemical groups

e.g. 1-3 methyl groups, acetyl groups, phosphate groups

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10
Q

Where are histone tails mostly methylated?

A

Lysines

  • up to 3 methyl groups can be added to 1 lysine
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11
Q

What happens to the chromatin when histone tails are methylated?

How does this affect gene expression?

A

Chromatin condenses

Genes repressed

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12
Q

What happens to the chromatin when histone tails are acetylated?

How does this affect gene expression?

A

Chromatin de-condenses
- histones move further apart

Genes expressed

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13
Q

How is heterochromatin self-propagating?

A

Chromatin modifications can spread along chromosomes

- methylated histones recruit more histone methylases

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14
Q

What is the ‘position effect’?

A

A normally active gene is silenced because of proximity to heterochromatin after DNA breakage & re-joining
(translocation events)

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15
Q

What are the other types of histone modifications?

A

> serine phosphorylation
Ubiquitination
SUMOlyation

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16
Q

What are the 4 types of regulatory proteins that bind to marked proteins to read the ‘histone code’?

A

> chromatin remodelling complexes
transcription activators
transcription repressors
DNA damage repair complexes (H2A.X)

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17
Q

What are epigenetics?

Who can they be passed between?

A

The study of heritable phenotype changes w/ no change in DNA sequence

> parent to offspring via germ cells
mother to daughter cells

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18
Q

What can cause epigenetic imprints?

A

> Exposure to pollutants
Stress
Drugs
Famine?

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19
Q

How can epigenetics lead to cancer?

A

Tumour suppressors hypermethylated
= silencer turned off
–> excessive cell division

20
Q

Describe DNA methylation in epigenetics

A

Adding methyl groups to DNA (CpG sites)

= represses gene transcription

21
Q

Give examples of when DNA methylation is essential for normal development

What is DNA methylation affected by?

A

> embryonic stem cells are largely de-methylated (pluripotent cells don’t require a lot of silencing)
methylation in cell differentiation

  • diet
  • environment
  • ageing
22
Q

What are the functional links between histone & DNA methylation?

A

> Gene silencing
Histone lysine methylation DNA methylation
Histone 3??
Maintenance methylation

23
Q

What is maintenance methylation?

A

Maintaining methylation patterns on newly-synthesised DNA strands after replication

e.g. for a liver cell to remain as a liver cell it must inherit epigenetic marks

24
Q

Describe the higher-order chromatin packing

A

30nm fibre of nucleosomes are assembled into loops on protein scaffold
–> form coils of heterochromatin

25
Q

What are the 2 examples of territories within the nucleus that represent the spatial arrangement of chromatin?

A

LADs = Lamina-associated domains

TADs = Topologically associated domains

26
Q

What are TADs formed by?

A

Cohesin

= ring-shaped protein complex that physically bundles chromatin

27
Q

What are TAD boundaries formed by?

A

CTCF
(=CCTC-binding factor)
= a transcription factor expressed in all cell types

28
Q

What are insulated neighbourhoods?

What happens in these regions?

A

Chromosomal loop structures formed by the physical interaction of 2 DNA loci bound by CTCF and co-occupied by cohesin

There is co-regulation of genes

29
Q

What are the 2 types of heterochromatin?

A

Facultative

Constitutive

30
Q

Describe facultative heterochromatin

A

= Parts of genome are silenced but have the potential to be expressed

> may switch between hetero- & euchromatin states
modification of histones or DNA

31
Q

Describe constitutive heterochromatin

A

= remains condensed throughout cell cycle

> highly repetitive sequences
may play role in chromatin structures
telomeres & centromeres

32
Q

What are telomeres?

A

Long repetitive sequences that protect the ends of chromosomes
- TTAGGG x 2,500 in humans
11 kb at birth –> 4 kb in old age

33
Q

Why do telomeres get shorter?

A

DNA replication enzymes cannot replicate v ends of DNA strands
- lose some telomeres w/ every cell division

34
Q

What is the ‘hayflick limit’?

A

no. of times a human cell population will divide before cell division stops

35
Q

When don’t telomeres get shorter?

Why?

A

If the cells express telomerase
e.g. germ cells, embryonic stem cells & cancer cells

They add telomere repeat sequences to the end of telomeres

36
Q

What is a centromere?

A

A specialised DNA sequence of a chromosome that links a pair of sister chromatids
= junction of replicated chromosomes

37
Q

What is the centromere the site of?

A

Where microtubules attach during mitosis

- at the kinetochore

38
Q

What can centromere instability result in?

A

Mis-segregation of chromosomes

–> embryonic death & cancer malignancy

39
Q

How is chromosome replication initiated?

A

Multiple origins on each chromosome
- each origin fires once per cell cycle
= ensures that DNA is copied only once

40
Q

How is chromosome replication timed?

A

Euchromatin replicated early

Heterochromatin replicated later

41
Q

What are the different changes in chromosome structure called?

A 
> deletion
> duplication 
> inversion
- paracentric
- pericentric 
> translocation
- balanced
- unbalanced
> dicentric chromosome
42
Q

Give an example of fragile regions for chromosomal breaks

A

TAD boundaries

43
Q

What are the 2 types of leukaemia?

A 
ALL = acute lymphoblastic leukaemia 
AML = acute myeloid leukaemia
44
Q

How is leukaemia caused?

A

1.translocation between chromosome 9 & 22
2. fusion of 2 genes:
> BCR = S/T kinase + Rho GEF
> ABL1 = NES + NLS
3. = BCR-ABL fusion protein

45
Q

What does the BCR-ABL protein do?

A 
Constitutively activate kinase
(= always on)
= oncogene
--> over-proliferation
=stem-like state
= resistance to cell death
46
Q

Which chromosome changes have occurred in human evolution?

A

Telomere-to-telomere fusion in chromosome 2
(all other primates have 2 chromosomes where we have chromosome 2)

Duplication of SRGAP@
–> changes in neurons
= sensory perception, memory & language

Cell Biology (23 decks)

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