University of Cambridge
Biochemistry
Professor Christine J Watson
Control of cell proliferation and death
Lecture 1: Cell cycle and regulation
➢ The human body maintains a delicate balance between cell proliferation and death.
➢ Without cell death an 80 year old would have:
• 2 million skin cells
• 2 tonnes of bone marrow and lymph nodes
• 16 km intestines
G1 phase:
• 6-12h – longest and most variable phase
• Early G1-phase occurs before the restriction point. This is mitogen dependent. Extrinsic
growth factors provide the stimulatory signal to proceed.
• There is growth in cell size as well as synthesis of proteins and RNA involved in DNA
replication.
• R-point: hyperphosphorylation of RB (retinoblastoma protein) by CDK-4D (Cyclin-
dependent kinase).
• G0: quiescence. No mitogens present so there is smaller lower metabolic activity. This
reduce protein synthesis.
• Nerve, muscle, liver, skin fibroblasts in G0 require extrinsic signals to divide. Platelet-
derived-growth-factor (PDGF) provides the signal.
• Embryonic stem cells: mitosis lasts 30m. There is no G1 / G2-phase. S-phase is rapid.
This causes division of egg cytoplasm into smaller cells.
• Late G1: no longer requires growth factors. The cell is committed to progression.
, • Checkpoint: CDK2 checks there is no damage to DNA before replication. Then
depending on the result chooses whether to repair the DNA damage or destroy the
mutated cell by apoptosis.
S phase:
• Lasts 6-8h
• Chromosomes and centromere replicate
G2 phase:
• Lasts 3-4h
• There is a check on the replicated DNA before mitosis
• Proliferation of proteins for mitosis which leads to a checkpoint
M phase:
• chromosome segregation
• nuclear division
• cytoplasmic division
• stimulated by cytokinesis
➢ Regulation of the cell cycle:
• components of regulation are synthesised and degraded at specific times
• at checkpoint they trigger repair or death
• CDK: 1,2,4,6: serines/threonine on proteins control initiation or regulation of cell cycle. They
are modulated by cyclins. They must be bound to be activated and then directed to target
proteins. But CDK levels are constant.
❖ CDK 7,8,9: regulate transcription
❖ Mitosis protein only available to phosphorylate during G2 – the accessibility of
substrates changes the course of chemical reactions.
o Cyclins are proteins with a cyclin box. They are synthesised and degraded in a
cyclical fashion during the cell cycle.
▪ Hunt et al experiments: fertilised/unfertilised eggs of sea urchins were
incubated in radioactive methionine
- Gel electrophoresis identified newly synthesised radiolabelled proteins
in the cell extracts
Biochemistry
Professor Christine J Watson
Control of cell proliferation and death
Lecture 1: Cell cycle and regulation
➢ The human body maintains a delicate balance between cell proliferation and death.
➢ Without cell death an 80 year old would have:
• 2 million skin cells
• 2 tonnes of bone marrow and lymph nodes
• 16 km intestines
G1 phase:
• 6-12h – longest and most variable phase
• Early G1-phase occurs before the restriction point. This is mitogen dependent. Extrinsic
growth factors provide the stimulatory signal to proceed.
• There is growth in cell size as well as synthesis of proteins and RNA involved in DNA
replication.
• R-point: hyperphosphorylation of RB (retinoblastoma protein) by CDK-4D (Cyclin-
dependent kinase).
• G0: quiescence. No mitogens present so there is smaller lower metabolic activity. This
reduce protein synthesis.
• Nerve, muscle, liver, skin fibroblasts in G0 require extrinsic signals to divide. Platelet-
derived-growth-factor (PDGF) provides the signal.
• Embryonic stem cells: mitosis lasts 30m. There is no G1 / G2-phase. S-phase is rapid.
This causes division of egg cytoplasm into smaller cells.
• Late G1: no longer requires growth factors. The cell is committed to progression.
, • Checkpoint: CDK2 checks there is no damage to DNA before replication. Then
depending on the result chooses whether to repair the DNA damage or destroy the
mutated cell by apoptosis.
S phase:
• Lasts 6-8h
• Chromosomes and centromere replicate
G2 phase:
• Lasts 3-4h
• There is a check on the replicated DNA before mitosis
• Proliferation of proteins for mitosis which leads to a checkpoint
M phase:
• chromosome segregation
• nuclear division
• cytoplasmic division
• stimulated by cytokinesis
➢ Regulation of the cell cycle:
• components of regulation are synthesised and degraded at specific times
• at checkpoint they trigger repair or death
• CDK: 1,2,4,6: serines/threonine on proteins control initiation or regulation of cell cycle. They
are modulated by cyclins. They must be bound to be activated and then directed to target
proteins. But CDK levels are constant.
❖ CDK 7,8,9: regulate transcription
❖ Mitosis protein only available to phosphorylate during G2 – the accessibility of
substrates changes the course of chemical reactions.
o Cyclins are proteins with a cyclin box. They are synthesised and degraded in a
cyclical fashion during the cell cycle.
▪ Hunt et al experiments: fertilised/unfertilised eggs of sea urchins were
incubated in radioactive methionine
- Gel electrophoresis identified newly synthesised radiolabelled proteins
in the cell extracts
