Lecture 11 Cell Cycle

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Cell cycle

Lecture 11
• In unicellular organisms, division of one cell reproduces the entire organism

• Multicellular eukaryotes depend on cell division for


• development from a fertilized egg
• growth
• repair

• Cell division is an integral part of the cell cycle, the life of a cell from
formation to its own division

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Distribution of Chromosomes During Eukaryotic Cell Division

• In preparation for cell division, DNA is replicated and the chromosomes condense
• Each duplicated chromosome has two sister chromatids (joined copies of the original
chromosome), attached along their lengths by cohesins
• During cell division, the two sister chromatids of each duplicated chromosome separate and
move into two nuclei
• Once separated, the chromatids are called chromosomes

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• Eukaryotic cell division consists of
• mitosis, the division of the genetic material in the nucleus
• cytokinesis, the division of the cytoplasm

• Gametes are produced by a variation of cell division called meiosis

• Meiosis yields non-identical daughter cells that have half as many


chromosomes as the parent cell

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Phases of the Cell Cycle

• The cell cycle consists of


• mitotic (M) phase (mitosis and cytokinesis)
• interphase (cell growth and copying of chromosomes in preparation for cell division)

• Interphase (about 90% of the cell cycle) can be divided into three phases:
• G1 phase (“first gap”)
• S phase (“synthesis”)
• G2 phase (“second gap”)

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The cell grows during all three phases, but chromosomes are duplicated only during the S phase
The eukaryotic cell cycle is regulated by a
molecular control system

• The frequency of cell division varies with the type of cell

• These differences result from regulation at the molecular level

• The cell cycle appears to be driven by specific chemical signals present in the
cytoplasm

• Cancer cells manage to escape the usual controls on the cell cycle

© 2018 Pearson Education Ltd.


• The sequential events of the cell cycle are directed by a distinct cell cycle control system,
which is similar to a clock
• The cell cycle control system is regulated by both internal and external controls
• The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is
received

© 2018 Pearson Education Ltd.


The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

• Two types of regulatory proteins are involved


in cell cycle control: cyclins and cyclin-
dependent kinases (Cdks)

• The activity of a Cdk rises and falls with


changes in concentration of its cyclin partner

• Expressions of cyclins depend on cell cycle


phases
• Cyclin D is expressed in response to mitogens

© 2018 Pearson Education Ltd.


The Cell Cycle Clock: the role of pRb
Stop and Go Signs: Internal and External
Signals at the Checkpoints

• Many signals registered at checkpoints come from cellular surveillance


mechanisms within the cell
• Checkpoints also register signals from outside the cell

• For many cells, the G1 checkpoint seems to be the most important


• If a cell receives a go-ahead signal at the G1 checkpoint, it will usually
complete the S, G2, and M phases and divide
• If the cell does not receive the go-ahead signal, it will exit the cycle, switching
into a nondividing state called the G0 phase

© 2018 Pearson Education Ltd.


• An example of an internal signal is that cells will not begin anaphase until all
chromosomes are properly attached to the spindle at the metaphase plate
• This mechanism ensures that daughter cells have the correct number of
chromosomes

© 2018 Pearson Education Ltd.


• External factors that influence cell division include specific growth factors
• Growth factors are released by certain cells and stimulate other cells to
divide

• In density-dependent inhibition, crowded cells will stop dividing


• Most cells also exhibit anchorage dependence – to divide, they must be
attached to a substratum

• Density-dependent inhibition and anchorage dependence check the growth


of cells at an optimal density
• Cancer cells exhibit neither type of regulation of their division

© 2018 Pearson Education Ltd.


Loss of Cell Cycle Controls in Cancer Cells

• Cancer cells do not respond normally to the body’s control mechanisms

• Cancer cells do not need growth factors to grow and divide:


• They may make their own growth factor
• They may convey a growth factor’s signal without the presence of the growth factor
• They may have an abnormal cell cycle control system

• Recent advances in understanding the cell cycle and cell cycle signaling have
led to advances in cancer treatment
• Coupled with the ability to sequence the DNA of cells in a particular tumor,
treatments are becoming more “personalized”

© 2018 Pearson Education Ltd.

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