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Cell Cycle

&
Cell Cycle Control

6. Cell Cycle and Cell Cycle Control


6.1 Phases of Cell Cycle
6.2 Special Apparatus of Mitosis
6.2.1 Chromatin/Chromosome
Chromatin DNA
Packing of Chromatin
Nucleosome, histone codes, epigenetic phenomena

6.2.2 Spindle

6.3 Cell Cycle Control


6.3.1 Core set of cell cycle control system
6.3.2 Cell cycle phases are triggered
sequentially
6.3.3 Check points in cell cycle
6.3.4 proto-oncogene and tumor suppressor
gene

6.1 Phases of Cell Cycle


6.1.1 Cell cycle
The cell cycle is process from the end of a
cell division to the start of the next cell
division. Cell cycle entails an ordered series
of macromolecular events that lead to cell
division and the production of two daughter
cells each containing chromosomes identical
to those of the parental cell.

6.1.2 Phases of cell cycle


The primary events of a mammalian cell cycle are
replication of chromosomes and their segregation
to daughter cells with extraordinarily high fidelity.
According to this, cell cycle can be divided into
INTERPHASE which includes G1, S, G2 phase and
DIVISION which is equal to M phase.
M phase includes MITOSIS and CYTOKINESIS
G0 phase: not divides, perform particular functions,
can return to the cell cycle when proper be
stimulated.

Phase of Cell Cycle

6.2 Special Apparatus of Mitosis


6.2.1 Chromatin/Chromosome
Chromatin DNA p228
There are three kinds of sequence elements in a
chromatin DNA
1 centromere
2 telomere
Several replication origins

replication origins
at which DNA polymerases and other
proteins initiate synthesis of DNA.
centromere
attach any chromosome that
contains it to mitotic spindle during
M phase and guarantees the proper
separation of chromosomes.
telomeres
permit a linear chromosome to be
completely replicated.

Packing of Chromatin
Nucleosome
octamer of H2A, H2B, H3, H4.
146bp binding DNA and 0~80bp linker DNA
Linker DNA are bound by H1 histone and are
sensitive to endonuclease.

(2)

histone codes, epigenetic phenomena


Modification of histone influence chromatin
structure participate in the regulation of
transcription.
(1) acetylation and deacetylation Lys-NH2 the
greater the acetylation, the less chromatin
condensation
(2) methylation Lys-NH2, Arg a process that
pevents acetylation
(3) phosphorylation Ser and Thr hydroxy
introducing a negative charge

Epigenetic: not depend on DNA sequence

6.2.2 Spindle p310

6.3 Cell Cycle Control


6.3.1 Core set of cell cycle control system
cyclin
cyclin dependent kinases, CDKs
cyclin dependent kinases inhibitors, CKIs
anaphase promoting complex, APC

cyclin A~H
G1 phase cyclin
cyclin C,D,E are only synthesized at G1 phase and
degraded at S phase
S phase cyclin
cyclin A are only synthesized at G1 phase and
degraded at M phase
M phase cyclin
cyclin B synthesized at S phase and degraded at the
end of M phase

cyclin dependent kinase

cyclin dependent kinases, CDKs


CDKs 1~8
a kind of protein kinases who will not be fully
activated unless they are binding with cyclins and
phosphorylated at proper residues at the same time.
CDKs are constantly synthesized in the whole cell
cycle but are selectively activated by different
cyclins and promote the shift of cell cycle phases.
Table p322,
maturation promoting factor, MPF =CDK1+cyclinB,
G2/M and M phase
START kinase, CDK4/6+cyclinD, G0/G1

cyclin dependent kinase inhibitors, CKIs


Selectively inhibit the kinase activity of CDKs by
binding to complex of CDKs and cyclins
p21, p27, p16

anaphase-promoting complex, APC


is a complex of several proteins which is activated
during mitosis to initiate anaphase.
The APC is an E3 ubiquitin ligase that marks target
proteins, e.g. cyclinB and cyclinA, for degradation by
the 26S proteasome. The irreversibility of
proteolysis is utilized by cells to give the cell cycle
directionality.

Cyclically Activated MPF


Mitosis Promoting Factor, MPF

Activation of MPF

6.3.3 Checkpoints in cell cycle


Cell cycle checkpoints exist at specific points
in the cell cycle in eukaryotic cells to prevent
them from progressing to the next phase of
the cell cycle in the event of DNA damage or
another condition which would make cell
division dangerous for the cell.

There are 3 main checkpoints which control


the cell cycle in eukaryotes.
G1 checkpoint, Restriction point
G2 check point
M check point

6.3.4 proto-oncogenes and


tumor suppressor genes
proto-oncogene
A normal gene which, when altered by
mutation, becomes an oncogene that can
contribute to cancer. Proto-oncogenes may
play an important role in many essential
physiological processes such as cell
proliferation, cell death and

tumor suppressor genes


Tumor suppressor genes are normal genes
that slow down cell division, repair DNA
mistakes, and tell cells when to die (a
process known as apoptosis or programmed
cell death). When tumor suppressor genes
don't work properly, cells can grow out of
control, which can lead to cancer.