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Nucleus and Nuclear Envelope
8/31/11 Second Lecture
14
Medical
Graduate
08/31/2011

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Term
What does the lamina do for the nuclear membrane?
Definition
It supplies structural support to the nuclear envelope. It also interacts with chromatin, modifying gene expression.
Term
Of the Lamin A, C, And 3 B genes, mutations in which have more drastic consequences?
Definition
Mutations in the 3 B genes tend to be lethal and as such are less commonly seen. A/C mutations cause disease but are not as frequently lethal.
Term
Explain how the nucleus is linked to the cytoskeleton
Definition
Parts of the cytoskeleton are attached to to Kash proteins in the membrane which are bound to Sun proteins which link to the nuclear lamina. The extracellular components can be actin, IF, or myofibrils
Term
What nuclear membrane feature allows for transport into and out of the nucleus?
Definition
Nuclear pore complex
Term
Describe the process of nuclear import
Definition
Proteins with side chains signaling the need to enter the nucleus are bound to transporter proteins to form a cargo complex. The transporter proteins bring the other protein into the nucleus. After this, the cargo complex reacts with Ran-GTP to release the transporter proteins from the original protein, which is now in the nucleus. The transporters are then transported back outside of the nucleus.
Term
What are histones?
Definition
proteins found in eukaryotic cell nuclei that bind to DNA and stick out (like tails) from the nucleosome structures. Interaction between histones and certain enzymes play a role in transcription initiation.
Term
How are nucleosomes ordered?
Definition
Nucleosomes are subsequently strung together into bead like chains of compacted chromatin, and subsequently packaged into higher order structures to reduce the physical size of the genome.
Term
What is the net result / main reason for nucleosmes and the higher order packaging of DNA?
Definition
Each DNA molecules is packaged such that it is 10,000 fold shorter then its extended length with histones
Term
What are heterochromatin?
Definition
Sections of chromatin that tend to exist on the periphery of the nucleus, are relatively transcriptionally inactive, and tend to replicate later
Term
what are euchromatin?
Definition
Transcriptionally active chromatin that tends to be located in the central of the nucleus
Term
How do transcription factors interact with the tightly packed chromosomes (2 ways)?
Definition
1. Mechanisms exist to open the compacted structure to allow access for transcription factors (chromatin-remodeling complex)
2. Enzymes interact with histone tails to promote the initiation of transcription
Term
How do HDAC inhibitors work?
Definition
HDAC inhibitors block enzyme activity that remove acetylations. This can lead to locking of the chromatin in certain desirable stages of the Histone Code (ex. such that cancer causing genes are silenced)
Term
What is the Histone code?
Definition
Acetylation, methylation, and phosphorylation of histones at different combinations of locations along the chromatin lead to separate chromatin states (ex. 3 potential acetylation sites. Acetylation at 1&3 could cause gene silencing, whereas 1&2 or 2&3 could promote gene expression).

The idea is that state of the chromatin can be read as a decipherable "code" if you know that state of all the histone locations.
Term
How do mutations in lamin and emerin genes potentially lead to muscular dystrophies?
Definition
1. Links between the nuclear lamina and cytoskeleton may be critical for structural integrity. Mutations in these can lead to failure under mechanical stress

2. Nuclear envelope proteins interact with chromatin and transcription factors and may influence gene expression. As such, alterations in these genes could lead to further altered gene expression.
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