The Nucleus

Question 1

What 3 things does compartmentalisation of the eukaryotic cell allow?

Answer 1

Protection of the DNA from a harsh cytosolic environment
Seperates nuclear and cytosolic enzymes
Provides a site for transcription

Question 2

What is the largest sub-nuclear body?

Answer 2

The nucleolus

Question 3

What is the space between the two membranes called?

Answer 3

The perinuclear space

Question 4

What is the nuclear lamina?

Answer 4

A dense fibrillar network inside the nucleus composed of intermediate filaments and membrane associated proteins

Question 5

What does the nuclear lamina do?

Answer 5

Regulates DNA replication and cell division as well as chromatin organisation and anchoring nuclear pore complexes

Question 6

What are the main mutations that cause laminopathies in?

Answer 6

Lamin A/C and emerin (nuclear laminar associated proteins)

Question 7

What is Emery-Dreifuss muscular dystrophy?

Answer 7

Affects cardiac and skeletal muscle. Causes joint deformaties and contractures as well as muscle wasting

Question 8

What is Hutchinson-Gilford Progeria syndrome?

Answer 8

A disease where the physical aspects of aging are accelerated, most patients have a point mutation in the LMNA gene.
Translation of lamin A lacking 50 amino acids.
Causes mechanical defects, thickening of the lamina, loss of heterochromatin and increased DNA damage increasing susceptibility to cancer.

Question 9

What is constitutive heterochromatin?

Answer 9

Never expressed

Question 10

What is the NPC freely permeable to?

Answer 10

Proteins smaller than 40kDa

Question 11

Describe the nuclear pore complex

Answer 11

8 composite rings of proteins at the cytoplasmic surface and inner surface
Connected by spoke proteins
From the outer ring there are 8 filaments emanating into the cytoplasm.
Membrane embedded section is associated with nuclear lamins.

Question 12

What are the 5 stages for nuclear import?

Answer 12

1. NLS recognition by importin complexed to Ran
2. Binds nuclear pore protein
3. Complex is translocated by sequential binding
4. GEF exchanges RanGDP for RanGTP releasing the protein
5. Importin-Ran/complex is re-exported and GAP hydrolyses GTPRan for GDPRan

Question 13

How many binding sites does importin a have and what are they?

Answer 13

2
Monopartite
Bipartite

Question 14

What recognises NESs?

Answer 14

Exportins

Question 15

What is Nup214 and what happens if it is mutated?

Answer 15

Facilitates export of NES bearing cargo

Mutation can lea to accumulation of proteins in the nucleus

Question 16

what is Triple A syndrome?

Answer 16

Mutations in ALADIN (NPC component)
Affects nuclear import of proteins involved in protecting DNA under oxidative stress
Causes mental retardation and autonomic dysfunction

Question 17

Give 3 viruses that bind NPCs

Answer 17

1. HBV
2. HSV
3. Adenovirus

Question 18

How does bulk mRNA exit the nucleus?

Answer 18

RNA splicing recrutis hTREX which is a complex of 20 proteins that marks the nuclear RNA for export and makes it stable which is squeezed through the pore

Question 19

What are mutations in hTREX associated with?

Answer 19

High grade tumours
A mutation enhances the formation of R loops (halt transcription and cause DNA damage), makes DNA-RNA hybrids when RNA binds a new DNA template