The Nucleus

Question 0

What are the three main clinical symptoms of laminopathies?

Answer 0

Progeria, lipodystrophy, skeletal/cardiac muscular dystrophy

Question 1

Emery-dreiffuss muscular dystrophy causes what clinical symptoms?

Answer 1

Contractures in joints, heart problems

Question 2

What type of mutation does Hutchinson-Gilford progeria have in the LMDA gene?

Answer 2

Point mutation causing 50 residue deletion in lamin A

Question 3

How viable are NPC mutations?

Answer 3

Not!

Question 4

Which protein is mutated in Triple A syndrome?

Answer 4

Integration of ALADIN porin in NPC

Question 5

What effect does the mutation in ALADIN have?

Answer 5

Import of apparataxin, ligase, ferritin heavy chain for repair of DNA following oxidative stress

Question 6

Which importin does HSV dock with?

Answer 6

B

Question 7

How does HBV virus injects DNA into nucleus?

Answer 7

Has NLSs to bind importins then passes through pore

Question 8

How does Adenovirus injects DNA?

Answer 8

Docks with CAN and Nup214 porins, Hsc70 and histones H1 to disassemble capsid

Question 9

What’s the formation of high grade tumours?

Answer 9

hTREX mutations cause RNA loop formation, DNA hybridisation and transcription is halted

Question 10

What is the structure of the nucleus?

Answer 10

6µm diameter

10% cell volume

Question 11

What is the function of the nucleus?

Answer 11

Separate enzymes
Transcription, translation for gene expression
DNA replication
Maintenance of genetic integrity

Question 12

What is the structure of the nuclear envelope?

Answer 12

Impermeable double membrane with pores
Outer bound to rER and cytoskeleton
Perinuclear space of 20-40nm
Inner membrane bound to lamina

Question 13

What is the nuclear lamina?

Answer 13

30-100nm network of intermediate filaments used to provide organisation and regulation of heterochromatin

Question 14

What is the main feature of laminopathies?

Answer 14

Irregular shaped nucleus due to poor filaments

Question 15

What are the 2 types of laminopathies?

Answer 15

Hutchinson Gilford Progeria

Emery-Dreiffus muscular dystrophy

Question 16

What is the structure of the Nuclear pore complexes?

Answer 16

symmetrical arrangement of 30-50 porins across both membranes
2 rings of 8 NUPs connected by spokes
projecting filaments

Question 17

How is the entry to the nucleus controlled?

Answer 17

NPC freely permeable to

Question 18

What is the structure of the NLS?

Answer 18

monopartite: K- K/R- X -K/R
bipartite: K/R-K/R -(10-12X)-(3-5)K/R

Question 19

What is the NES?

Answer 19

LxxxLxxLxL

Question 20

What are the NPC mutations?

Answer 20

NUP214 (no export)
NF-KB
Triple A

Question 21

How is mRNA exported?

Answer 21

Splicing deposits EJCs
Tailing
Capping recruits hTREX
hTREX ALY component binds TAp-p15 to dock to NPC
100-150A rod 
Reforms structure in cytoplasm

Question 22

When is hTREX mutated?

Answer 22

Highly resistant cancers

Question 23

How does export affect functionality of mRNPs?

Answer 23

Changes conformation of Balbani ring to bind to ribosome