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BB10005 > Chromosomes > Flashcards

Chromosomes Flashcards

(48 cards)

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1
Q

each chromosome

A

one linear strand of dna

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2
Q

Humans have how many

A

46

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3
Q

diploid

A

2n

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4
Q

Haploid

A

1n

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5
Q

Karyotype

A

number, size and shape of chromosomes eg XY and XX

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6
Q

The packing problem

A

each cell has 2m of dna in length

Fit into a nucleus of 6 um diameter

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7
Q

DNA packaging in chromosomes

A

Many levels of

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8
Q

Nucelosome

A

1st level of organisation in a chromosome
Bead on a string
Each nucleosome 147 bps wound 1.67 times per bead
Protein core made of histones
Between beads there is linker DNA with a H1 histone
Nucleosomes further coil up to form chromatin fibres

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9
Q

Histones

A

made up of 4 subunits which make up a tetramer
2 tetramers join together to make an octamer (bead)
Each octamer has 2 copies of each histone

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10
Q

nucleosomes are dynamic

A 
Chromatin remodelling factors:
Nucelosomes can be slid along the dna strand
Exchange histone octamers or subunits
Remove core histones
to expose DNA strand
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11
Q

HIstone tails

A

Can be modified by addition of chemical groups

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12
Q

Modification of histone tails

A

1-3 methyl groups added
acetyl groups
mostly on lysines

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13
Q

Methylation

A

chromatin condenses

gene repression

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14
Q

Acetylation

A

Chromatin decondenses

gene expression

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15
Q

Heterochromatin is self propagating

A

chromatin modification spreads along chromosomes

Methylated histone can recruit methyl transferases to modify neighbouring histones

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16
Q

Position effect

A

normally active gene silenced because of proximity to heterochromatin after dna breakage and re-joining

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17
Q

Other modification

A

serine phosphorylation
ubiquitination
SUMOlyation

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18
Q

What regulatory proteins bind to marked histones to ‘read the histone code’

A

chromatin remodelling complexes
transcription activators
Transcription repressors
DNA damage repair complexes

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19
Q

Epigenetics

A

modifications give rise to this

changes in the genome that are inherited but don’t involve changes in the DNA sequence

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20
Q

Epigenetic imprints passed on how

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A
  • from mother to daughter cells
  • parent to child
  • passed along in tissues over course of life from: exposure to pollutants, stress, drugs
  • cancer: tumour supressors hypermethylated, leading to excessive cell division
21
Q

Where are methyl groups added to on DNA to repress transcription

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A

sequences of dna that have lots of C-G repeats, known as CpG islands

22
Q

Dna methylation is essential for

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A

normal development:

  • embryonic stem cells de-methylated mostly
  • occurs during differentiation
  • affected by diet, environment and ageing
23
Q

Functional links between histone methylation and dna methylation

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A

Both give rise to gene silencing
Methylated histones can methylate the DNA and vice versa
Involves Histone 3, important for ‘maintenance methylation’

24
Q

Maintenance methylation

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A

pattern of methylation needs to be maintained after dna is replicated on the new strands

25
DNA packaging in chromosomes
Chromatin fibres loop and coil around each other on a protein scaffold Assembled into loop regions. Loop regions not associated with a protein scaffold are available for transcription: euchromatin Coiled again into heterochromatin
26
LADs
lamina associated domains
27
TADS
topologically associated domains Sections of looped and coiled dna that are bundled together by cohesin Boundaries formed by CTCF
28
Cohesin
Protein complex that is a dimer that forms a ring structure | Wraps around DNA to induce loops
29
CTCF
CCCTC- binding factor | TF expressed in all cell types
30
Insulated neighbourhoods
The genes in these loops co-regulated | One or more per TAD
31
Types of heterochromatin
Facultative and Constitutive
32
Facultative heterochromatin
Potential for gene expression Modification of histones or DNA May switch between hetero and euchromatin states
33
Constitutive heterochromatin
Condensed throughout cell cycle Highly repetitive sequences May play a role in chromatin structure Telomeres and centromeres
34
Telomeres
Long repetitive sequences of DNA on the ends of chromosomes Protect the ends of DNA strands Born with 11kb telomeres, when old 4kb telomeres
35
Why do telomeres get shorter?
Dna repls enzymes can't replicate very ends of dna strands so lose a little with every cell division known as Hayflick limit
36
Exception to telomeres getting shorter
If cells express telomerase | eg germ cells (eggs and sperm), embryonic stem cells, cancer cells
37
Centromeres
Large arrays of repetitive dna At junction of sister chromatids Where microtubules attach during mitosis (kinetochore) Instability of centromeres can result in mis-segregation of chromosomes: - embryonic death - cancer malignancy
38
Chromosome replication and origins
multiple origins in repl | Each origin fires once per cycle- ensures DNA only copied once
39
Replication timing
Eurochromatin repl early, start of S phase | Hetero later
40
changes in chromosome structure
Various ways Most common are deletions and substitutions- break in the chromosome and dna damage repair ligates and misses out a chunk of dna Or during synthesis there could be synthesis of extra dna, which joins in a after breakage during rejoining Or inversions- paracentric (away from the centromere) or pericentric (towards) Or fusions- lose whole elements of the chromosome Or translocation- sections of pair of chromosomes broken and rejoined- unbalanced/balanced
41
TAD boundaries
fragile regions for chromosome breaks
42
ALL
acute lymphoblastic leukaemia
43
AML
Acute Myeloid Leukaemia
44
AML and ALL
result from translocation between chromosome 9 and 22 | Breakpoint Cluster Region in 22 is region that breaks
45
What happens in AML and ALL
fusion of 2 genes BCR- S/T kinase and Rho GEF ABL1- tyrosine kinase (NES and NLS)
46
BCR ABL fusion protein
constitutively active kinase (always on) Means it is an oncogene Leads to over-proliferation, stem- like state and resistance to cell death
47
Chromosome changes in human evolution
We have 46, primates have 48 2 chromosomes involved in a telomere to telomere fusion evet to form our chromosome 2 Also 2 duplications of SRGAP2- resulted in expansion of neocortex (growth of grey matter) Led to higher functions eg sensory perception, memory and language
48
summary
dna wound around histones to form nucleosomes

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