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How Cells Divide

•HeLa’s immortal cells (named after Henrieta Lack’s


cells)
•Attempts by George and Margaret Gey of Johns
Hopkins University to culture human cells were
unsuccessful
•Assistant was about to give up when Henrieta’s cells
began to divide at an alarmingly fast rate.
•Cells could divide outside the human body- study of
disease without using HUMAN subjects was possible!
•Important contribution to cell division studies- up to
now!
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Bacterial Cell Division
• Bacteria divide by binary fission.
➢the single, circular bacterial chromosome is
replicated
➢replication begins at the origin of replication and
proceeds bidirectionally
➢new chromosomes are partitioned to opposite ends
of the cell
➢a septum forms to divide the cell into 2 cells

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Eukaryotic Chromosomes
Eukaryotic chromosomes –
➢linear chromsomes
➢every species has a different number of
chromosomes
➢composed of chromatin – a complex of DNA and
proteins
➢ heterochromatin – not expressed
➢ euchromatin – expressed regions

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Eukaryotic Chromosomes
Chromosomes are very long and must be condensed to
fit within the nucleus.
➢nucleosome – DNA wrapped around a core of 8
histone proteins
➢nucleosomes are spaced 200 nucleotides apart along
the DNA
➢further coiling creates the 30-nm fiber or solenoid

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Eukaryotic Chromosomes
The solenoid is further compacted:
➢radial loops are held in place by scaffold proteins
➢scaffold of proteins is aided by a complex of
proteins called condensin

karyotype: the particular array of chromosomes of an


organism

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Eukaryotic Chromosomes

• Chromosomes must be replicated before cell


division.
➢Replicated chromosomes are connected to each
other at their kinetochores
➢cohesin – complex of proteins holding replicated
chromosomes together
➢sister chromatids: 2 copies of the chromosome
within the replicated chromosome

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Eukaryotic Cell Cycle
• The eukaryotic cell cycle has 5 main phases:
1. G1 (gap phase 1)
2. S (synthesis)
3. G2 (gap phase 2) interphase
4. M (mitosis)
5. C (cytokinesis)
• The length of a complete cell cycle varies greatly
among cell types.

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STAGES IN THE CELL CYCLE
Interphase

• Interphase is composed of:

• G1 (gap phase 1) – time of cell growth

• S phase – synthesis of DNA (DNA replication)


• - 2 sister chromatids are produced

• G2 (gap phase 2) – chromosomes condense


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Interphase
• Following S phase, the sister chromatids appear to
share a centromere.
• In fact, the centromere has been replicated but the 2
centromeres are held together by cohesin proteins.
• Proteins of the kinetochore are attached to the
centromere.
• Microtubules attach to the kinetochore.

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Interphase
• During G2 the chromosomes undergo condensation,
becoming tightly coiled.

• Centrioles (microtubule-organizing centers)


replicate and one centriole moves to each pole.

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Mitosis
Mitosis is divided into 5 phases:
1. prophase
2. prometaphase
3. metaphase
4. anaphase
5. telophase

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Mitosis
Prophase:
➢chromosomes continue to condense
➢centrioles move to each pole of the cell
➢spindle apparatus is assembled
➢nuclear envelope dissolves

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Mitosis
Prometaphase:
➢chromosomes become attached to the spindle
apparatus by their kinetochores
➢a second set of microtubules is formed from the
poles to each kinetochore
➢microtubules begin to pull each chromosome
toward the center of the cell

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Mitosis
Metaphase:
➢microtubules pull the
chromosomes to align
them at the center of the
cell
➢metaphase plate:
imaginary plane through
the center of the cell
where the chromosomes
align
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Mitosis
Anaphase:
➢removal of cohesin proteins
causes the centromeres to
separate
➢microtubules pull sister
chromatids toward the poles
➢in anaphase A the
kinetochores are pulled
apart
➢in anaphase B the poles
move apart 28
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Mitosis
Telophase:
➢spindle apparatus disassembles
➢nuclear envelope forms around each set of sister
chromatids
➢chromosomes begin to uncoil
➢nucleolus reappears in each new nucleus

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Cytokinesis
Cytokinesis – cleavage of the cell into equal halves
➢in animal cells – constriction of actin filaments
produces a cleavage furrow
➢in plant cells – plasma membrane forms a cell plate
between the nuclei
➢in fungi and some protists – mitosis occurs within
the nucleus; division of the nucleus occurs with
cytokinesis

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Control of the Cell Cycle
The cell cycle is controlled at three checkpoints:
1. G1/S checkpoint
➢ the cell “decides” to divide
2. G2/M checkpoint
➢ the cell makes I Party Monday And Tuesday
a commitment to mitosis
3. late metaphase (spindle) checkpoint
➢ the cell ensures that all chromosomes are
attached to the spindle in preparation for anaphase

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Figure 12.16

G0
G1 checkpoint

G1 G1

(a) Cell receives a go-ahead (b) Cell does not receive a


signal. go-ahead signal.
Control of the Cell Cycle
CDks drive the cell cycle

• cyclin-dependent kinases (Cdks) – enzymes that


drive the cell cycle
➢activated only when bound by a cyclin
• cyclins – proteins produced in synchrony with the
cell cycle
➢ regulate passage of the cell through cell cycle
checkpoints

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Figure 12.17
M G1 S G2 M G1 S G2 M G1
MPF activity
Cyclin
concentration

Time
(a) Fluctuation of MPF activity and cyclin concentration
during the cell cycle

Cdk

Degraded
cyclin G2 Cdk
checkpoint
Cyclin is
degraded
Cyclin
MPF

(b) Molecular mechanisms that help regulate the cell cycle


Control of the Cell Cycle
• At G1/S checkpoint:
➢G1 cyclins accumulate
➢G1 cyclins bind with Cdc2 to create the active G1/S
Cdk
➢G1/S Cdk phosphorylates a number of molecules
that ultimately increase the enzymes required for
DNA replication

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Control of the Cell Cycle
• At the spindle checkpoint:
➢the signal for anaphase to proceed is transmitted
through anaphase-promoting complex (APC)
➢APC activates the proteins that remove the cohesin
holding sister chromatids together

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Control of the Cell Cycle
• Growth factors:
➢can influence the cell cycle
➢trigger intracellular signaling systems
➢can override cellular controls that otherwise inhibit
cell division
• platelet-derived growth factor (PDGF) triggers
cells to divide during wound healing
• Growth factors are examples of external signals at
checkpoints

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• A clear example of external signals is density-
dependent inhibition, in which crowded cells stop
dividing
• Most animal cells also exhibit anchorage
dependence, in which they must be attached to a
substratum in order to divide

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CANCER is a failure of cell cycle control

➢CANCER cells exhibit neither density-dependent


inhibition nor anchorage dependence
➢Cancer is a failure of cell cycle control.
➢A normal cell is converted to a cancerous cell by a
process called transformation
➢Cancer cells that are not eliminated by the immune
system form tumors, masses of abnormal cells
within otherwise normal tissue

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➢If abnormal cells remain only at the original site, the
lump is called a benign tumor
➢Malignant tumors invade surrounding tissues and
can metastasize, exporting cancer cells to other
parts of the body, where they may form additional
tumors

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• Two kinds of genes can disturb the cell cycle when
they are mutated:
1. tumor-suppressor genes
2. proto-oncogenes
1. Tumor-suppressor genes:
➢prevent the development of many cells containing
mutations
➢for example, p53 halts cell division if damaged
DNA is detected
➢p53 is absent or damaged in many cancerous cells

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Proto-oncogenes:
➢some encode receptors for growth factors
➢some encode signal transduction proteins
➢become oncogenes when mutated
➢oncogenes can cause cancer when they are
introduced into a cell

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https://www.youtube.com/watch?v=U5vAO_f2LDQ
https://www.khanacademy.org/test-prep/mcat/cells/cellular-division/v/loss-of-cell-cycle-
control-in-cancer

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