It deals with basics about the mechanism and changes happening in chromosome during cell division. You can understand the changes with the help of diagrams in this slide

1. Cell division
mitosis
Muthu bharathi
I Msc., Biotechnology

3. • Cell cycle
M phase
Inter phase
M phase
Mitosis
Cytokinesis
Interphase
G1, S phase( DNA synthesis),G2 phases
DNA synthesis was first proposed by alma howard,Stephen pelc
in 1953

4. Check points
• Crucial protective response
• Leland hartwell,Ted weinert 1988
• As a part of cell cycle
• Surveillence mechanism that halt the cell cycle when
• 1. Any of the chromosomalDNA is damaged
• 2.Certain critical processes such as DNAreplication during S phase or
chromosomal alignment during M phase do not occur properly
• Several proteins of checkpoint machinery are work during abnormal
condition that are not taking role in normal cell cycle
• Check points activated throughout the cell cycle
• Check point proteins first identified in yeast cells

5. Importance of check point
• If the DNA is damaged beyond repair, the checkpoint mechanism can
transmit a signal that leads either to
• (1) the death of the cell or
• (2) its conversion to a state of permanent cell cycle arrest (known as
senescence).

6. Mitosis
• Mitosis ( Greek) thread
• Term coined by walther flemming 1882
• Thread represents chromosome
• Process of nuclear division
• DNA molecule of each chromosome segregated into two nuclei
• maintains the chromosome number and generates new cells
• Cytokinesis– splitting of dividing cell
partitioning of cytoplasm into two cellular packages
• possess a genetic content identical to each other and to
the mother cell from which they arose.

9. • Mitosis can take place in either haploid or diploid cells.
• Haploid mitotic cells are found in fungi, plant gametophytes, and a few
animals (including male bees known as drones).
• Mitosis is a stage of the cell cycle when the cell devotes virtually all of its
energy to a single activity—chromosome segregation.
PROPHASE
duplicated chromosomes are segregated
Mitotic machinery is assembled
Chromosomal compaction (condensation) occurs in early prophase
Converting chromosome into shorter, thicker molecule for
segregation
Because, interphase chromosomes are responsible for transcription
and replication and not suitable for segregation
Protein for chromosome condensation is condensin

10. • Chromatin of interphase is fiber like structure nearly 30 nm in dia

11. • Chromosome scaffold occur in interphase
stage
• Histone proteins are removed
• Loops formed by non histone proteins
• chromosome scaffold are dispersed
within the nucleus,
possibly forming part of the nuclear matrix
cohesion
• Form ring around sister chromosome
• interphase replication G2 phase
cohesion cohesion
mitotic phase

12. Centromere & kinetochore
• Centromere - repeated DNA sequence ,act as a binding site for specific
proteins
• Kinetochore – proteinaceous, button like structure, outer surface of
centromere at each chromatid
• Assemble during prophase
(1) the site of attachment of the chromosome to the dynamic microtubules
of the mitotic spindle
(2) the residence of several motor proteins involved in chromosome motility
(3) a key component in the signaling pathway of an important mitotic
checkpoint

13. Kinetochore protein
• Ringshaped protein complex called Dam1 whose inner
diameter of 32 nm is large enough to comfortably
surround a microtubule

14. • Floating grip
• Maintain the Attachment of kinetochore to microtubule
• 2 motor proteins Ndc80, CENP-E
FORMATION OF THE MITOTIC SPINDLE ( bundle of microtubule)
Centrosome cycle occur ( separation of right angled centrosome by enzyme seperase) ie.,
they lose their close association
Duplication of centrosome occur prior to mitosis (G1 –S phase)
Which become a Pair of mother – daughter centrosome by Cdk2 proteins
Step1 - sunburst arrangement / aster around each centrosome (early prophase)
Step2 – separation and movement of centrosome towards opposite pole of cell
Stpe3 – stretching of microtubule and increase in number
Bipolar spindle

15. The Dissolution of the Nuclear Envelope and
Partitioning of Cytoplasmic Organelles
• Interaction between the spindle and chromosomes is made possible
by the breakdown of the nuclear envelope at the end of prophase
• Major components of the nuclear envelope—the nuclear pore
complexes, nuclear lamina, and nuclear membranes which are
initiated by phosphorylation of mitotic kinases cyclin B-Cdk1
Dynein molecules are responsible for torning nuclear pore in nuclear
envelope

16. Prometaphase
• Mitotic spindle assembly completed
• Chromosomes scattered in Center of cell
• Free (plus) ends of the microtubules are seen to grow and shrink in a
dynamic fashion
• Microtubule catches kinetochore
congression
chromosome toward the center of mitotic spindle, midway between
the poles

17. Microtubule behaviour
• When attached to kinetochore, elongated microtubule become
shortened whereas the shortened tubules become elongated to the
sister kinetochore
• This is due to the pulling force ( tension )
• Spindle fiber – each kinetochore attached
to 20-30 microtubule

18. Metaphase
• 3 groups of microtubule in metaphase stage
• Astral
• Chromosomal
• polar

19. • Astral microtubule
radiate outward from centrosome
help position of spindle apparatus in the cell
determine the plan of cytokinesis
Chromosomal microtubule
extend between centrosome and kinetochore
pulling force is due to spindle fiber
Polar microtubule
extend from centrosome to chromosome
microtubule of opposite centrosome may overlap
form a structural basket
maintain the mechanical integrity of spindle

20. Microtubule Flux in the Metaphase Spindle
• Microtubules are in dynamic state

22. Anaphase
• Sister chromatids split apart
• Move towards opposite poles
APC Cdc20 activated prior to metaphase ubiquitinates anaphase
Inhibitor protein ,securin ( secure the attachment of sister chromatids)
Activate seperase cleave cohesion(hold sister chromatids)
Thus anaphase starts

23. Complexes of anaphase
• SCF & APC – add ubiquitinin to protein at different stages of cell cycle,
targeting them for destruction by proteasomes
• SCF activates during interphase
• APC ( Anaphase promoting complex) activates during metaphase
contains dozen of core proteins
adapter protein Cdc20, Cdh1
determining substrate selection of APC
end of mitosis Cdc20 inactivated
Cdh1 take part for substrate selection of APC

24. • SAC – spindle assembly checkpoint,
prevents the binding of APC till
metaphase
• APCCdh1 activity during early G1 helps
maintain the low cyclin–Cdk activity

25. Events of anaphase
• Movement of chromosomes to opposite poles
• They move slowly (1µm for 1 minute)
• Metaphase (subunits added to plus end, keeping the length constant)
• Anaphase (subunits lost from plus end, shortening of chromosomal length)
• Anaphase A – movement of chromosome toward poles
• Anaphase B – movement of spindle fibres
for elongation of microtubule, subunits are added to +end

26. Forces for anaphase
• Depolymerization of microtubule
occur at both +, - ends
+ end “chew up chromosome”
- end “transport of chromosome towards poles”
Depolymerizing kinesin protein,present at both +,- ends
• “ATPdependent, kinesin-mediated depolymerization forms the basis
for chromosome segregation during mitosis.”

27. Spindle assembly checkpoints(SAC)
• Operates at transition between metaphase and anaphase
• Reveal when chromosome fails to align properly
• There may be delay for onset of anaphase