THE CELL CYCLE AND ITS SAFEGUARDS AGAINST CANCER
SOURCE: PZ Myers (Pharyngula)
Dividing cells follow a cycle.
- Most cells are in G1 (Gap 1), doing what cells do.
- Then under control of clock-like changes in specific genes, they can enter the S (synthesis) phase, when their DNA is replicated,
- followed by a G2 phase (gap 2),
- and then an actively dividing mitotic or M phase.
Each of these phases has a checkpoint where a battery of proteins survey the state of the cell and either permit the process to proceed, or block it if there are problems.
In extreme cases, the checkpoint proteins can determine that the cell is so irreparably damaged that the only option is suicide, and the cell will self destruct.
This is the process that cancer needs to disrupt if it is to continue; cancer cells typically have damaged DNA or aberrant signals flying everywhere that ought to be triggering all kinds of alarms in the checkpoint system, and either stopping cell division immediately, or activating repair mechanisms that fix the damage, or just killing the corrupted cell immediately.
One of the most critical points in this cycle is called the R or Restriction point.
- Prior to the R point, the cell is sensitive to external signals that can induce cell division;
- after this point, the cell no longer pays attention to those signals, because it is on a rigidly programmed track towards completing cell division.
The R point is that last fateful moment of decision before the cell commits to dividing.
Standing at this point is an essential guardian of the cell cycle, pRb. This protein is an inhibitor of cell division, acting as a tumor suppressor gene. It’s the guard at the gate, and it must be satisfied that all is well in the cell before it will allow division to continue.
pRb’s default mode is to stop cell division, but it receives signals from a wide array of pathways that can tell it to stand down and let the process continue.
Control of this gene is complicated because it is so essential to well-regulated cell division: look at it here, standing sentry just above the yellow R point, with all these other pathways talking to it.
I think you can see how this gene can contribute to cancer when it’s defective. Shoot the guard, open the gate wide, and allow cell divisions to proceed unchecked.
This passage is a part of PZ Myers’ much longer critique of an article on the evolution of cancer by two physicists, Paul Davies and Charles Lineweaver, ‘Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors” (Phys. Biol. 8 015001-015008).