Cell cycle, cell death and cancer biology
Đã giới thiệu| English | Ý nghĩa |
|---|---|
| checkpoint/ˈtʃekpɔɪnt/ | checkpoint |
| apoptosis/əpəpˈtəʊsɪs/ | apoptosis |
| driver mutation | driver mutation |
| two-hit | two-hit |
| tumour suppressor gene | tumour suppressor gene |
The two biggest decisions
- Dividing and dying are a cell's most costly decisions, and checkpoints guard both.
- Cancer is the slow failure of those gates, and every gate is a system you have already met: repair, signalling and regulation.
The cycle and its gates
- A typical human cell cycle takes 24 h: G1 (growth, ~11 h), S (DNA copying, ~8 h), G2 (~4 h) and M (mitosis, ~1 h).
- Checkpoints 检查点 sit at G1/S (the restriction point), G2/M and spindle assembly. Cells can leave into resting G0, or into apoptosis 细胞凋亡, programmed death carried out by caspases.
Put the cell-cycle phases in order, starting just after division.
Độ khó 3/5 · 200 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
11 + 8 + 4 + 1 = 24 h for a typical cycling human cell.
The guardian of the genome
- After DNA damage, p53 pauses the cycle at G1/S for repair, or sends the cell into apoptosis if the damage is too great.
- To become a cancer, a cell needs about 4–7 driver mutations 驱动突变, plus endless division (telomerase) and escape from apoptosis.
Why is p53 called the guardian of the genome?
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
p53 enforces the G1/S checkpoint: repair first and divide later, or die. Cancer must get past this gate.
Thirty silent doublings
- After $n$ unchecked divisions there are $2^{n}$ cells. A 1 cm³ tumour weighs about 1 g, about $10^{9}$ cells, and $2^{30} = 1.07\times10^{9}$.
- So a tumour you can just find is already thirty generations old. It did not appear fast; it grew silently for years.
A tumour of about 10⁹ cells grew from one cell. About how many doublings old is it?
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
2³⁰ = 1.07 × 10⁹. A tumour you can just detect has been growing silently for years, which is why screening intervals matter.
Worked example: the mutation lottery
- About 6 mutations survive each division (unit 1.3). Most land in non-coding DNA and do nothing; the chance that one disables a given gate is tiny.
- But a body makes about $10^{16}$ divisions in a lifetime, and each driver makes the next one more likely. That is why cancer becomes more common with age.
The 1 cm³ tumour (10⁹ cells) keeps doubling. How many more doublings until it reaches 1 kg (10¹² cells)?
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
10¹² / 10⁹ = 1000 ≈ 2¹⁰, so 10 more doublings: a third as many as it took to become detectable. A lethal tumour is about 40 doublings old.
Worked example: one gate down from birth
- (Fictional family) Sarcoma, breast cancer and a brain tumour appear early across three generations. Each patient inherited one faulty p53 copy (a Li–Fraumeni pattern).
- Every cell starts one gate down; one chance hit on the second copy removes the checkpoint. This is the two-hit 二次打击 logic of tumour suppressor genes 抑癌基因.
What do tumour suppressor genes typically need before their gate fails?
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
As in the fictional Li–Fraumeni family: inherit one bad copy, lose the second by chance in one cell, and the gate falls.
Three common slips
- "Apoptosis is passive death." It is active, programmed and uses ATP; necrosis is the messy kind.
- Oncogenes and tumour suppressors are the same. An oncogene gains a function with one hit; a tumour suppressor loses its function after two.
- "Fast growth means fast cycling." Usually fewer cells die, rather than cells dividing faster.
Match each term to its description.
Độ khó 2/5 · 140 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Oncogenes are accelerators stuck on; tumour suppressors are brakes that must both fail. Apoptosis is tidy and uses ATP; necrosis is not.
Fast-growing tumours are fast mainly because their cells divide much faster than normal cells.
Độ khó 1/5 · 100 xu + phần thưởng nhỏ khi hoàn thành lần đầu tiên hôm nay
Usually fewer cells die (escape from apoptosis) rather than each cycle being much shorter.
Recap
- A 24 h cycle with three checkpoints; G0 and apoptosis are the exits.
- p53 is the damage gate; tumour suppressors need two hits, oncogenes one.
- $2^{30}\approx10^{9}$ cells = 1 cm³ = thirty silent doublings.