Perhaps the most characteristic feature of life is the ability to replicate, to make copies of itself. 

During the process of cell replication, the genetic material must be replicated.  The two strands of the DNA molecule separate, and each serves as a template for generating a new strand.  

Changes in the DNA that accumulate prior to, or which occur during replication, are passed on to the daughter cells.  

These daughter cells are build by capturing energy and matter from the environment. 

If we inoculated a culture with a few bacteria, within a few hours they will have transformed components of the medium into millions of copies of themselves.

If we look at these cells with a microscope, we find that they do not grow haphazardly.

They appear remarkably uniform in both size and shape. They grow to a certain size and then divide.

Cells monitor and control their size.  

For example, consider the single celled eukaryote, Amoeba proteus – these organisms divide only after they have grown to a characteristic size.

Using microsurgical methods, it is possible to keep cells small by simply repeatedly cutting off parts of the cell.  After the cell heals, it grows.

If you do this repeatedly, the cell grows but never divides.  This type of experiment argues that the cell does not use time to decide to divide, but rather size.

How does the cell know when it has reached the correct size, how does it known when to divide?

Studies on yeasts (eukaryotic microorganisms) have identified mutations that lead to cells that are consistently larger or smaller than the usual, or wild type phenotype.

The ability to find such mutations implies that an active, genetically encoded system controls when cells divide.

• In amoeba, what experiment suggested that a cell must reach a certain size before it divides?  What might the controls be for such an experiment?
• Consider a culture of bacteria, which might have an evolutionary advantage, a mutation that led to cells that are larger or smaller than normal?  
• What factors might determine optimal cell size?
• What disadvantages would such a mutation have?

Bacterial cell cycles:  The replication of a cell, or an organism, can be thought of as a cycle.  Somewhat arbitrarily, we place the beginning of this cycle with the decision to replicate the genetic material, the DNA.

This is a critical decision.   DNA replication involves the unwinding of the DNA and a set of highly interdependent and coordinated processes.

Consider the following catastrophic scenario.  A cell begins replicating its DNA, but before it completes the process it runs out of resources -- ATP levels fall and the other deoxyribonucleotide triphosphates needed to synthesize DNA are in short supply.

Under these conditions replication forks will stop and the DNA will be left unwound and incompletely replicated.  This is a situation that is likely to lead to massive DNA damage.  

optional: DNA replication.

To avoid this possibility, cells tightly regulate the initiation of DNA replication.

This decision is known as start; once made, the cell begins on the path to DNA replication.

In bacteria start involves the molecular decision to build a replication initiation complex.

The initiation complex consists of proteins that associate with a specific DNA sequence, the origin of replication or ori.

There is a single ori in the bacterial chromosome and acts like a gene. In E. coli this gene is called OriC. For a DNA molecule to replicate, it must have at least one functional origin of replication.

This is where the replication bubble initiates; the two replication forks move away from one another and around the chromosome. The forks collide in the region of the chromosome known as the terminator or ter.

At the end of replication, two sister chromosomes are entangled with one another, they are concatenated.

They are untangled by the enzyme topoisomerase, which can pass one double-stranded DNA molecule through another.

Once the replicated chromosomes are separated, the cell can be divided into two.

A septum assembles at the center of the cell.

This molecular "purse string" is linked to the inner surface of the plasma membrane.

As it contracts, it pulls the membrane together and separates the two cells.

When growing under optimal conditions bacteria can divide as fast as once every 15-20 minutes.

• Even though it does not produce a product, it is possible to view OriC as a gene.  What happens to a bacterial cell if there is a mutation in OriC?  
• Suggest a reason why mutations that disrupt the gene that encodes topoisomerase might lead to an increased mutation rate in other genes. 

While most prokaryotic cells have a single circular chromosome, most eukaryotes typically have multiple linear chromosomes, and each chromosome has multiple origins of replication.  Each chromosome is a single DNA molecule. 

The DNA in each chromosome must be completely replicated and the copies segregated so that each daughter cell receives one and only one complete copy of each chromosomal DNA molecule.

The complexity of the eukaryotic cell, makes mitosis and cell division, known as cytokinesis, more mechanically intricate than the analogous processes in prokaryotes.  

As in the case of bacterial cells (above), eukaryotes have a cell cycle. 

Start is located in the period known as G₁ phase; the period during which DNA synthesis occurs is known as S phase. 

The period between the end of S and the beginning of mitosis is known as G₂ phase. 

Mitosis itself is known as M phase. 

The length of the cell cycle can various tremendously, from hours to years.

Cells that are not actively dividing are said to be in G_o.   Some cells enter G_o and never divide again – these cells are said to be terminally differentiated.

We will leave the mechanical and molecular details of mitosis and cytokinesis to more advanced classes in cell biology, what is critical to remember is that they provide a complete copy of the genome to each daughter cell (mitosis) and they divide the cell into two (cytokinesis). 

Checkpoints:  The process of chromosome replication and segregation is so critical to the future of the replicated cell that its accuracy is checked in a number of ways. 

In bacteria, there is a DNA damage checkpoint that inhibits DNA replication until damaged DNA is repaired.

The process of chromosome replication, segregation and cell division is much more complex in eukaryotes, and so there are more possibilities for error.

There are correspondingly more checkpoints. These include

• checking that DNA synthesis is complete
• checking that the DNA is undamaged, and that if damaged, repaired
• checking that all of the chromosomes are attached to the molecular machinery that segregates chromosomes to daughter cells, the mitotic spindle.

• What happens to the two daughters if mitosis is not accurate, e.g. if one cell receives two copies of a chromosome, while the other receives none?
• What happens if the cell divides before DNA replication is completed? 
• What might happen, if a cell arrests at a checkpoint, but cannot fix the problem?   Is this a serious problem for unicellular organisms?  how about multicellular organisms?