AP Biology
Notes:  Mitosis

                                                    
Mitosis:

* Unicellular organisms,  the division of one cell to form two reproduces an entire organism 
* In multicellular organisms, cell division allows:
            Growth and development from the fertilized egg
             Replacement of damaged or dead cells

Cell division
    * Precisely replicates its DNA
    * Allocates the two copies of DNA to opposite ends of the cell
    * Separates into two daughter cells containing identical hereditary information
    * Usually proceeds in to sequential steps: nuclear division (mitosis) and division 
       of the cytoplasm (cytokinesis).  Not all cells undergo cytokinesis following mitosis


M phase, the shortest part of the cell cycle and the phase during which the cell 
divides, includes:
    1.  Mitosis-Division of the nucleus
    2. Cytokinesis-Division of the cytoplasm

Interphase, the nondividing phase includes most of the a cell's growth and 
metabolic activates
                   
    * Is about 90% of the cell cycle
    * Is a period of intense biochemical activity during which the cell grows and 
    copies its chromosomes in preparation for cell division
    Consists of three periods
            1.  G1 phase= First growth phase (G stands for gap
            2.  S phase-synthesis phase occurs when DNA is synthesized as 
                 chromosomes are duplicated (S stands for synthesis)
            3.  G2 phase- second growth phase



Mitosis is a continuous process, but for ease of description, mitosis is usually divided
 into five stages: prophase, prometaphase, metaphase, anaphase, and telophase

  G2 of interphase:

    A well-defined nucleus bounded by a nuclear envelope
    One or more nucleoli
    Two centrosomes adjacent to the nucleus (formed earlier by replication of a single 
    centrosome)
    In animals, a pair of centrioles in each centrosome
    In animals, a radial microtubular arraay (Aster) around each pair of centrioles
    Duplicated chromosomes that cannot be distinguished individually due to loosely 
    packed chromatin fibers (Chromosomes were duplicated earlier in S phase).


Prophase
                       


In the nucleus:
    Nucleoli disappear
    Chromatin fibers condense into discrete, observable chromosomes composed 
    of two identical sister chromatids joined at the centromere

In the cytoplasm:
    Mitotic spindle forms.  It is composed of microtubules between the two 
    centrosomes or microtubule-organizing centers
    Centrosomes move apart, apparently propelled along the nuclear surface by 
    lengthening of the microtubule bundles between them.


Prometaphase
                                                


    Nuclear envelope fragments, which allows microtubules to interact with the 
    highly condensed chromosomes
    Spindle fibers (bundles of microtubules) extend from each pole towards the 
    cell's equator.
    Each chromatid now has a specialized structure, the kinetochore, located at 
    the centromere region.
    Kinetochore microtubules become attached to the kinetochores and put the 
    chromosomes into agitated motion
    Nonkinetochore microtubules radiate from each centrosome toward the 
    metaphase plate without attaching to chromosomes.  Nonkinetochore microtubules 
    radiating from one pole overlap with those from the opposite pole


Metaphase
                                               
  

        Centrosomes are positioned at opposite poles of the cell
        Chromosomes move to the metaphase plate, the plane equidistant between the 
        spindle poles
        Centromeres of all chromosomes are aligned on the metaphase plate
       The long axis of each chromosome is roughly at a right angle to the spindle axis
        Kinetochores of sister chromatids face opposite poles, so identical chromatids 
        are attached to kinetochore fibers radiating form opposite ends of there parent cell 
       Entire structure formed by nonkinetochore microtubules plus kinetochore microtubules 
        is called the spindle.


Anaphase

                                                   
   
Anaphase is characterized by movement It begins when parried centromeres of 
    each chromosome move apart.
        *Sister chromatids split apart into separate chromosomes and move towards 
          opposite poles of the cell
        *Because kinetochore firs are attached to the centromeres, the chromosomes 
          move centromere first in a "V" shape
        *Kinetochore microtubules shorten at the kinetochore end as chromosomes 
          approach the poles
        *Simultaneously the poles of the cell move farther apart, elongating the cell


Telophase and Cytokinesis
                         

        Nonkinetochore microtubules further elongate the cell
        Daughter nuclei begin to form at the two poles
        Nuclear envelopes form around the chromosomes from fragments of the parent 
        cell's nuclear envelope and portions of the endomembrane system.
        Chromatin fiber of each chromosome uncoils and the chromosomes become less 
        distinct.

    By the end of telophase:
        Mitosis, the equal division of one nucleus into two genetically identical nuclei, 
        is complete Cytokinesis has begun and the appearance of two separate 
        daughter cells occurs shortly after mitosis is complotted.

The mitotic spindle distributes chromosomes to daughter cells

Many of the events of mitosis depend on the formation of a mitotic spindle.  
The mitotic spindle forms in the cytoplasm form microtubules and associated proteins.
        *Microtubules of the cytoskeleton are partially disassembled during spindle formation
        *Spindle microtubules are aggregates of tow proteins, α and β-Tubulin
         *The assembly of spindle microtubules begins in the centrosome or microtubule 
            organizing center.

The chronology of mitotic spindle formation is as follows:
    Interphase:  The centrosome replicates to form two centrosomes located just outside 
                         the nucleus
    Prophase:    The two centrosomes move farther apart.
                         Spindle microtubules radiate form the centrosomes, elongating at the 
                         end ways from their centrosome.


     Kinetochore microtubules from one pole may attach to a kinetochore, moving the 
    chromosome toward that pole.  This movement is checked when microtubules form the 
    opposite pole attach to the chromosome's other kinetochore.

    The chromosome oscillates back and forth until it stabilizes and alights at the 
    cell's midline

    Microtubules can remain attached to a kinetochore only if there is opposing tension 
    from the other side.  It is this opposing tension that stabilizes the microtubule-
    kinetochore connection and allows the proper alignment and movement of 
    chromosomes at the cell's midline.

Metaphase.  All the duplicated chromosomes align on the cell's midline, or   
                     metaphase plate

Anaphase.
  The chromosome's centromeres split and the sister chromatids move 
                   as separate chromosomes toward opposite ends of the cell.  The
                   kinetochore and nonkinetochore microtubules direct the segregation 
                   of the chromosomes The kinetochore microtubules shorten during anaphase 
                   by depolyerizing at their kinetochore ends; pulling the chromosomes poleward.
                   The mechanism of this interaction between kinetochores and microtubules may 
                   involve microtubule-walking proteins similar to dynein that "walk" a chromosome 
                   along the shortening microtubules
                      

Cytokinesis
   
First a cleavage furrow forms as a shallow groove in the cell surface near the 
    old metaphase
    A contractile ring of actin microfilamnts forms on the cytoplasmic side of the furrow 
    this ring contracts until it pinches the parent cell in two.
    Finally the reaming mitotic spindle breaks the the two cells become completely separate.

Regulation of the Cell cycle

Human skin cells dived frequently
Liver cells only dived in appropriate situations, such as wound repair
Nerve, muscle and other  specialized cells do not dived in mature humans.
The cell-cycle control system has checkpoints in the G1, G2, and M phases of 
the cell cycle.
                       
   

 For many cells the G1 checkpoint (known as the "restriction point" in the 
 mammalian cells) is the most important

        * A go-ahead signal usually indicates that the cell will complete the cycle and divide
        * In the absence of a go-ahead signal, the cell may exit the cell cycle switching to 
          the nondividng state called G0 phase.
        * Many cells other the human body are the G0 phase.  Muscle and nerve cells will 
           remain in G0 until they die.  Liver cells may be recruited back to the cell cycle 
           under certain cues, such as growth factors.


Kinase Control:

*Protein kinases are enzymes that catalyze the transfer of a phosphate group from 
  ATP to a target protein.
*Phosphorylation, in turn, induces a conformational change that either activates or 
  inactivates a large protein.
*These regulatory proteins are named cyclins, because their concentrations change 
  cyclically during the cell cycle.
*Protein kinases that regulate cell cycles are cyclin-dependent kinases (Cdks); they 
  are active only when attached to a particular cyclin
*Even though the Cdk concentration stays the same throughout he cell cycle, it 
  activity changes in response to the  changes in cyclin concentration
*Cyclin's rhythmic changes in concentration regulate MPF, so as cyclin concentration 
  rises and falls, the amount of active MPF changes in a similar way

MPF
        Cyclin is produced at a uniform rate throughout the cell cycle, and it accumulates 
        during interphase
        Cyclin combines with Cdk to form active MPF, so as cyclin concentration rises 
        and falls, the amount of active MPF changes in a similar way.
        MPF phosphorylates proteins that participate in mitosis and initiates the 
        following process:
            *Chromosome condensation during prophase
            *Nuclear envelope dispersion during prometaphase
            *MPF activates proteolytic enzymes
            *The proteolytic enzymes destroy cyclin which leads to the reduction of 
            *MPF activity (the Cdk portion of MPF is not degraded)
            *The proteolytic enzymes also are involved in driving the cell cycle past the 
              M-phase checkpoint, which controls the onset of anaphase.