Cell cycle and cancer corelation

1. Cell Cycle
Jaineel Dharod
Dept. of Pharmacology

2. Introduction
A cycle of events that a cell completes from one division to the next is
called the cell cycle.

4. Cell Cycle
6
Interphase: time between divisions
– G1, S, and G2
Mitosis: division of the chromosomes
Cytokinesis: division of the cytoplasm
Checkpoints in the cell cycle regulate cell division

7. G0 phase (quiescence)
G0 is a resting phase where the cell has left the cycle and has
stopped dividing. The cell cycle starts with this phase.
Eg: Skin cells, Neurons, etc.

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Interphase
●
G1
– Begins immediately after division
– New organelles formed
– End of G1, cell has doubled in size
●
S phase
– Duplicate copy of each chromosome
●
G2 phase
– Cell prepares to begin mitosis

9. Mitosis
• The process by which cells reproduce themselves, resulting in
daughter cells that contain the same amount of genetic material as the
parent cell.

10. Stages of Mitosis

11. Stages of Mitosis: Prophase
●
Replicated chromosomes condense and
become visible.
●
46 chromosomes composed of two sister
chromatids.
●
Nuclear membrane breaks down.
●
Spindle fibers form.

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3
Stages of Mitosis: Prophase

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4
Stages of Mitosis: Metaphase
●
Chromosomes, with spindle fibers attached,
move to middle of cell

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Stages of Mitosis:Anaphase
●
Centromeres divide.
●
Converts each sister chromatid to a
chromosome.
●
Chromosomes migrate to opposite ends of cell.
●
Complete set of 46 chromosomes at each end
of cell.

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Stages of Mitosis: Anaphase

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Stages of Mitosis:Telophase
●
Final stage of mitosis
●
Chromosomes unwind
●
Spindle fibers break down
●
Nuclear membrane re-forms

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8
Cytokinesis: Last Stage of Cell Cycle
●
Cell membrane constricts and divides cell into
two daughter cells with 46 chromosomes

18. Identical Daughter Cells

19. CellDifferentiation

20. Checkpoints of Cell Cycle
●
●
Internal and external signals
Either stimulates or inhibits a metabolic event.

23. Cyclins / CDKs /CKIs
Cyclin dependent kinases:
If no cyclin present, cell is
arrested in a phase and no
further process takes place.

24. Cell-cycle checkpoints
●
●
●
Restriction point
– Regulate initiation of
DNA replication
G2-M checkpoint
– Checks DNA
damage
Spindle checkpoint
– Checks chromosome
alignment

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DNA DamageCheck Point
●
DNA Damage can be 'checked' at various
sites. (Before 'S', During 'S', After 'S' )
● Detected by DNA bound proteins ATM & ATR.
●
Transcription factor p53 is activated after
damage is detected. (guardian of genome)
● It activates p21 ( a CKI) that blocks CDK2/4.

27. Replication Checkpoint
●
●
●
Before entering the M phase of the cycle.
If some errors in the replication of the genome
is identified by chk1 and CDC25C.
The activation of CDK1 is prevented thus
causing prevention of M phase of cycle.

28. Spindle Integrity checkpoint
microtubules in green, chromosomes in blue, and kinetochores in pink

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Spindle IntegrityCheckpoint
●
●
●
●
●
The most dangerous time for a cell.
Aligning duplicated chromosomes by attaching
them to bipolar attachments to the spindle.
The sensors of this check point are present in
the kinetochores.
APC/C Cofactor ~ CDC20 is inhibited unless
there is equal tension on both the sides.
CDC20 when active inhibits 'securin' which
then enables the seperation process.

30. Cell Cycle and Cancer
• Cancer is partly a disease of uncontrolled proliferation.
• Cell cycle and check point genes are found misregulated /
mutated in cancer.
• Protooncogenes
• Tumor Supressor Genes

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1
CancerCells

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Protooncogene /Oncogene
●
●
●
●
A proto-oncogene is a normal gene that can
become an oncogene due to mutations.
The resultant protein : oncoprotein.
The mutations are generally dominant.
Examples: SRC, RAS, WNT, MYC, cSIS
GBMPancreas colon breast burkitts

33. Tumor SupressorGene
• ~ anti-oncogene.
• Mutations in these genes cause loss of function, thus
causing malignancy.
• Mutations are generally recessive, thus heterozygosity is
necessary for mutation to be apparent. 'two-hit hypothesis'
• Examples: pRb, p53, APC, BRCA

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Proto-Oncogene RAS
●
Produces RAS protein that:
– Attaches to inside of plasma membrane
– Is part of a pathway that turns on cell division
– Is signaled by growth factors from outside the cell
●
RAS mutations in many types of cancer,
including colon, lung, pancreatic, and stomach
cancer
●
Mutant RAS stuck “on” and produces
uncontrolled cell division.

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BRCA1
●
Described in 1970s after analyzing pedigrees
of 1,500 families.
● In 1990, identified in chromosome 17
●
Dominantly inherited, carry one mutant copy
gene, develop breast cancer if other copy
mutates
82%: breast cancer
44%: ovarian cancer
Another gene BRCA2 is in Chromosome 13, rare and causes susceptibility to breast cancer.

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Thank You