To-morrow, and to-morrow, and to-morrow...
To-morrow, and to-morrow, and to-morrow,
Creeps in this petty pace from day to day,
To the last syllable of recorded time;
And all our yesterdays have lighted fools
The way to dusty death. Out, out, brief candle!
Life's but a walking shadow, a poor player
That struts and frets his hour upon the stage
And then is heard no more. It is a tale
Told by an idiot, full of sound and fury
Signifying nothing.
Are we brief candles? What is the clock that turns yesterdays into tomorrows lighting our way to dusty death? If you believe the telomere theory of ageing, we are candles, quite literally. The candle burns every time our cells divide. The chromosomes are capped by repetitive DNA sequences (telomeres); a short stretch is being lost every time a cell divides. When the telomeres become too short, the cells cannot divide any more. Some birds can elongate the telomeres in their somatic cells; mammals can't. This burning candle is said to protect us from cancer by tumor supression, but it also makes it certain that we'll die. The choice (in the absence of disease, harm, and predation) boils down to dying from the programmed senescence or inevitable cancer. Some choice...
But there are better players around. Bacteria have circular DNA; there is no "candle" to burn. They can go on multiplying to the last syllable of recorded time, but can they tell apart today and tomorrow?
The cyanobacteria can. Their 24 hour circadian clock works in the dark, keeping time for a few weeks. No one believed that such a clock might be possible: the bacteria divide much faster than the period of the clock; yet the rhythm persists during the division. Actually, it persists in vitro, in a solution containing ATP: there are three kaiABC proteins that run through a 24 hr cycle of phosphorylation of the kaiC hexamer. The clock itself is chemical (it is a system of reactions with a double-negative-feedback loop) but it is also a global switch: the transcription of 800 genes (out of the total of 2700) is turned on in the morning and turned off in the evening.
How can one protein affect the transcription of 800 genes? There is strong indication that kaiC changes the topology of DNA (the oscilloid model). Bacterial DNA is a loop that is further rolled into supercoiled domains. The clock protein flips the DNA between two superhelical states. In one of these states the coils are looser, so the translation is faster. Like a flower, the DNA of a bacterium opens in the morning and closes in the evening -- to-morrow, and to-morrow, and to-morrow -- for what has already been 3.8 billion years.
Isn't it great that someone upon this stage can always look forward to another tomorrow?
http://download.journals.elsevierhealth.com/pdfs/journals/0014-5793/PIIS0014579309009144.pdf
http://www.sciencemag.org/cgi/reprint/sci;318/5851/757.pdf
http://www.cas.vanderbilt.edu/johnsonlab/publications/reprints/pmid11463211.pdf
http://onlinelibrary.wiley.com/doi/10.1002/jcb.20519/pdf
http://www.pnas.org/content/106/52/22564.full
http://www.pnas.org/content/104/47/18819.full
Creeps in this petty pace from day to day,
To the last syllable of recorded time;
And all our yesterdays have lighted fools
The way to dusty death. Out, out, brief candle!
Life's but a walking shadow, a poor player
That struts and frets his hour upon the stage
And then is heard no more. It is a tale
Told by an idiot, full of sound and fury
Signifying nothing.
Are we brief candles? What is the clock that turns yesterdays into tomorrows lighting our way to dusty death? If you believe the telomere theory of ageing, we are candles, quite literally. The candle burns every time our cells divide. The chromosomes are capped by repetitive DNA sequences (telomeres); a short stretch is being lost every time a cell divides. When the telomeres become too short, the cells cannot divide any more. Some birds can elongate the telomeres in their somatic cells; mammals can't. This burning candle is said to protect us from cancer by tumor supression, but it also makes it certain that we'll die. The choice (in the absence of disease, harm, and predation) boils down to dying from the programmed senescence or inevitable cancer. Some choice...
But there are better players around. Bacteria have circular DNA; there is no "candle" to burn. They can go on multiplying to the last syllable of recorded time, but can they tell apart today and tomorrow?
The cyanobacteria can. Their 24 hour circadian clock works in the dark, keeping time for a few weeks. No one believed that such a clock might be possible: the bacteria divide much faster than the period of the clock; yet the rhythm persists during the division. Actually, it persists in vitro, in a solution containing ATP: there are three kaiABC proteins that run through a 24 hr cycle of phosphorylation of the kaiC hexamer. The clock itself is chemical (it is a system of reactions with a double-negative-feedback loop) but it is also a global switch: the transcription of 800 genes (out of the total of 2700) is turned on in the morning and turned off in the evening.
How can one protein affect the transcription of 800 genes? There is strong indication that kaiC changes the topology of DNA (the oscilloid model). Bacterial DNA is a loop that is further rolled into supercoiled domains. The clock protein flips the DNA between two superhelical states. In one of these states the coils are looser, so the translation is faster. Like a flower, the DNA of a bacterium opens in the morning and closes in the evening -- to-morrow, and to-morrow, and to-morrow -- for what has already been 3.8 billion years.
Isn't it great that someone upon this stage can always look forward to another tomorrow?
http://download.journals.elsevierhealth.com/pdfs/journals/0014-5793/PIIS0014579309009144.pdf
http://www.sciencemag.org/cgi/reprint/sci;318/5851/757.pdf
http://www.cas.vanderbilt.edu/johnsonlab/publications/reprints/pmid11463211.pdf
http://onlinelibrary.wiley.com/doi/10.1002/jcb.20519/pdf
http://www.pnas.org/content/106/52/22564.full
http://www.pnas.org/content/104/47/18819.full