The Nucleus Flashcards
What are the three main clinical symptoms of laminopathies?
Progeria, lipodystrophy, skeletal/cardiac muscular dystrophy
Emery-dreiffuss muscular dystrophy causes what clinical symptoms?
Contractures in joints, heart problems
What type of mutation does Hutchinson-Gilford progeria have in the LMDA gene?
Point mutation causing 50 residue deletion in lamin A
How viable are NPC mutations?
Not!
Which protein is mutated in Triple A syndrome?
Integration of ALADIN porin in NPC
What effect does the mutation in ALADIN have?
Import of apparataxin, ligase, ferritin heavy chain for repair of DNA following oxidative stress
Which importin does HSV dock with?
B
How does HBV virus injects DNA into nucleus?
Has NLSs to bind importins then passes through pore
How does Adenovirus injects DNA?
Docks with CAN and Nup214 porins, Hsc70 and histones H1 to disassemble capsid
What’s the formation of high grade tumours?
hTREX mutations cause RNA loop formation, DNA hybridisation and transcription is halted
What is the structure of the nucleus?
6µm diameter
10% cell volume
What is the function of the nucleus?
Separate enzymes
Transcription, translation for gene expression
DNA replication
Maintenance of genetic integrity
What is the structure of the nuclear envelope?
Impermeable double membrane with pores
Outer bound to rER and cytoskeleton
Perinuclear space of 20-40nm
Inner membrane bound to lamina
What is the nuclear lamina?
30-100nm network of intermediate filaments used to provide organisation and regulation of heterochromatin
What is the main feature of laminopathies?
Irregular shaped nucleus due to poor filaments
What are the 2 types of laminopathies?
Hutchinson Gilford Progeria
Emery-Dreiffus muscular dystrophy
What is the structure of the Nuclear pore complexes?
symmetrical arrangement of 30-50 porins across both membranes
2 rings of 8 NUPs connected by spokes
projecting filaments
How is the entry to the nucleus controlled?
NPC freely permeable to
What is the structure of the NLS?
monopartite: K- K/R- X -K/R
bipartite: K/R-K/R -(10-12X)-(3-5)K/R
What is the NES?
LxxxLxxLxL
What are the NPC mutations?
NUP214 (no export)
NF-KB
Triple A
How is mRNA exported?
Splicing deposits EJCs Tailing Capping recruits hTREX hTREX ALY component binds TAp-p15 to dock to NPC 100-150A rod Reforms structure in cytoplasm
When is hTREX mutated?
Highly resistant cancers
How does export affect functionality of mRNPs?
Changes conformation of Balbani ring to bind to ribosome
