Lecture series D6 cont
“Cell cycle and cell division”
notes based on Alberts et al 4th ed. (2002) Chapters 17 and
18
prepared by T. J. Newman, November 17, 2005
this document not
for public use – all images copyright Garland Science Publishing 2002
http://www.microscopyu.com/moviegallery/livecellimaging/index.html
(thanks to Sebastian Sandersius)
INTRODUCTION
·
Cells are not
created de novo – new cells arise
from division of existing cells
·
The process of
cell duplication and division is known as the cell
cycle
·
In unicellular
organisms, the cell cycle creates a new unicellular organism
·
In multicelluar
organisms, the cell cycle furnishes new cells for maintaining the functionality
of the organism
o
in the human
body, millions of new cells are being created each second
·
Key events in the
cell cycle of all cells are
o
chromosome duplication
o
chromosome segregation
o
cell division
·
An array of intracellular regulatory
proteins monitors the various stages of the cell
cycle, with important checkpoints
o
e.g. to ensure
that replicated DNA is undamaged
o
we will not cover
the cell cycle control system in this
lecture
·
Extracellular regulatory signals also control the cell cycle in multicellular
organisms
o
thus allowing the
organism to regulate the numbers and types of cells from which it is comprised
·
Some
extracellular signals cause a given cell to undergo apoptosis,
i.e. programmed cell
death
OVERVIEW OF THE CELL CYCLE
·
The cell cycle is
first divided into two periods
o
M phase, which includes nuclear division (mitosis) and cell division (cytokinesis)
o
interphase (that part of the cell cycle which is not contained
in M phase)
o
in mammals, the
cell cycle of many cells has a duration of roughly 10-12 hours, with M phase
requiring roughly 1 hour
·
Interphase is
itself divided into three periods:
o
G1 – gap phase 1
o
S – S phase (DNA
replication)
o
G2 – gap phase 2
·
During the gap
phases, the cell monitors internal and external cues before committing to DNA
synthesis and/or mitosis
·
If conditions are
unfavorable, cells may delay progress through G1
o
in some cases
cells will enter a special dormant phase, G0
·
Even though the
duration of the phases varies considerably for cells from different organisms,
the control system is highly conserved
o
thus, biologists
have learned a great deal about the control system in human cells by studying
simpler systems, e.g. yeasts
·
A major class of
genes involved in cell cycle regulation are the cdc genes (cell-division-cycle genes)
·
Another important
cell-cycle regulatory gene is p53: this inhibits
the cell cycle if there is damage to DNA
o
mutations to p53
are implicated in origins of cancer
·
An example of
extremely rapid cell division occurs in early embryos
·
E.g. in the frog
embryo:
o
initial egg is
1mm in diameter (contains 105 times more cytoplasm than human egg)
o
cleavage
divisions occur rapidly – 12 divisions (leading to 4096 cells) in ~ 7 hours
o
in these
divisions, only DNA synthesis is occurring
o
there are no
detectable gap phases
APOPTOSIS
·
Apoptosis, or programmed cell death, is a controlled “suicide”
of a cell (apoptosis, Gr – “falling off”)
·
The amount of
apoptosis in higher organisms is surprisingly large
o
e.g. in the
developing vertebrate nervous system, 50% of nerve cells die soon after
creation
o
in adult humans,
billions of cells die in the bone marrow each hour
·
Other examples of
cell death:
o
during
development, digits are formed from cell death
in the interdigital space (see below for example
of mouse paw)
o
in transitioning
from tadpole to frog, massive cell death occurs in the tadpole tail
·
In a normal adult
organism, cell death must balance cell creation in order to establish an
equilibrium of cell numbers
·
If a cell dies
because of injury it typically spills its contents into the surrounding medium
o
this is called cell necrosis
o
the spillage is
potentially damaging to neighboring cells
·
A cell which dies
via apoptosis does so in a “tidy” fashion
o
the cell shrinks
o
cytoskeleton collapses
o
nuclear envelope disassembles
o
nuclear DNA breaks into
fragments
o cell surface displays indicators which target the cell for ingestion by neighboring cells, or by a