The Nucleus

 Nuclear envelope

• Nuclear membranes act as barriers that prevent the free passage of molecules between the nucleus and the cytoplasm.
• Two concentric membranes (phospholipid bilayers) are called the inner and outer nuclear membranes.
• The outer nuclear membrane is continuous with the ER so the space between the inner and outer membrane is directly connected with the lumen of the ER. This space is termed the perinuclear space.
• Channels through membrane provided by nuclear pores. Selective traffic of proteins and RNAs through these pores.
•  Under the inner membrane you have the nuclear lamina. The nuclear lamina is a fibrous meshwork that provides structural support to the nucleus. Network of proteins known as lamins. The lamins associate with each other to form filaments. In addition to providing structural support, the nuclear lamina is thought to serve as a site of chromatin attachment. Chromatin within the nucleus is organized into large loops of DNA, some of which appear to be bound to the nuclear envelope. The lamins may help to mediate this interaction. (text pages 144-151 and 326-331)

• Nucleus has internal structure that organizes the genetic material and localizes some nuclear functions to discrete sites.
• The nucleolus is the site at which the rRNA genes are transcribed and ribosomal subunits are assembled.
• Additional organization suggested by the organization of chromosomes and by the potential localization of functions such as DNA replication and pre-mRNA processing to distinct nuclear domains.

•  G1 - period between last mitotic division and start of DNA synthesis. Active period of gene transcription.
• S- DNA is replicated
• G2- cell further prepares to divide
• M- Nuclear division (mitosis)
• mitosis: prophase, metaphase, anaphase, and telophase
• C -Cytoplasmic division (cytokinesis)
•  During G1 through S, chromatin is dispersed and fills the entire nucleus Makes sense - don't want it to be too condensed for transcription and replication.
•  Following S and leading up to metaphase of mitosis (100X condensation).
• Metaphase chromosomes represent the most condensed phase.
• Important because it allows the chromosomes to be faithfully segregated into daughter cells. None of the DNA is transcriptionally active in this conformation.

• The centromere looks like a constriction in the chromosome. Point where two sister chromatids are joined together. Also point of attachment of the spindle fibers during mitosis.
•  These centromeric regions contain specific DNA sequences and bound proteins. When proteins are bound the structure is termed a kinetochore.

• Sequences at the very ends of the chromosome.
• Play critical role in chromosome replication and maintenance.

• During interphase- some of the chromatin (~10% of total chromatin) remains highly condensed and is termed heterochromatin - this DNA is transcriptionally inactive.
•  Two types:

constitutive heterochromatin
Contains DNA sequences which are never transcribed [such as highly repetitive satellite DNA sequences].
 facultative heterochromatin
Contains sequences that are not transcribed in the particular cell under examination but are transcribed in other cell types.
 
Examples:
B lymphocytes are the only cells which express the immunoglobulin genes. During interphase, the Ig genes would be in euchromatin form in B lymphocytes. In all other cell types, the Ig genes would be in the form of heterochromatin.]

 The phenomenon of X chromosome inactivation also provides an example of the role of heterochromatin in gene expression. In many animals, including humans, females are XX and males are XY. The X chromosome contains thousands of genes that are absent from Y. Thus, females have twice as many X chromosome genes as males. However, males and female cells have equal amounts of the proteins encoded by the X chromosome. One of the 2 X chromosomes in female cells is inactivated by being converted to heterochromatin early in development.
 

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