S Phase: What Happens During this Subphase of the Cell Cycle?

Have you ever wondered how your body grows or how it heals an injury? The short answer is cell division.

It’s probably no surprise that this vital cell biology process is highly regulated – and therefore includes many steps. One of these important steps is the S phase of the cell cycle.

What Is the Cell Cycle?

The cell cycle – sometimes called the cell division cycle – comprises the steps a eukaryotic cell must complete in order to divide and produce new cells. When a cell divides, scientists call the original cell the parent cell and the cells produced by the split the daughter cells.

Mitosis and interphase are the two basic parts that make up the cell cycle. Mitosis (sometimes called M phase) is the portion of the cycle where actual cell division occurs. Interphase is the time between divisions when the cell does the work to get ready to divide, such as growing and replicating its DNA.

The time it takes to complete the cell cycle depends on the type of cell and the conditions. For example, most human cells require a full 24 hours to divide, but some cells are fast-cycling and divide much more quickly.

Scientists who grow the cells that line the intestines in the lab sometimes see those cells complete the cell cycle every nine to ten hours!

Looking at Interphase

The interphase portion of the cell cycle is much longer than the mitosis portion. This makes sense because a new cell must absorb the nutrients it needs to grow and replicate its DNA and other vital cell machinery before it can become a parent cell and divide via mitosis.

The interphase part of the cell cycle includes sub-phases called Gap 1 (G1 phase), Synthesis (S phase) and Gap 2 (G2 phase).

The cell cycle is a circle, but some cells exit the cell cycle temporarily or permanently via the Gap 0 (G0) phase. While in this sub-phase, the cell expends its energy performing whatever tasks that cell type normally does, rather than dividing or preparing to divide.

During the G1 and G2 sub-phases, the cell grows larger, replicates its organelles and gets ready to divide into daughter cells. S phase is the DNA synthesis phase. During this portion of the cell cycle, the cell replicates its entire complement of DNA.

It also forms the centrosome, which is the microtubule-organizing center that will eventually help the cell pull apart the DNA that will be divided between daughter cells.

Entering S Phase

The S phase is important because of what takes place during this portion of the cell cycle and also because of what it represents.

Entering S phase (passing through the G1/S transition) is a major checkpoint in the cell cycle, sometimes called the restriction point. You can think of it as the point of no return for the cell since it is the last opportunity for the cell to stop cell proliferation, or cell growth via cell division. Once the cell enters S phase, it is destined to complete cell division, no matter what.

Because the S phase is the major checkpoint, the cell must tightly regulate this portion of the cell cycle using genes and gene products, such as proteins.

To do this, the cell relies on keeping a balance between pro-proliferative genes, which urge the cell to divide, and tumor suppressor genes, which work to stop cell proliferation. Some important tumor suppressor proteins (encoded by tumor suppressor genes) include p53, p21, Chk1/2 and pRb.

S Phase and Replication Origins

The major work of the S phase of the cell cycle is replicating the entire complement of DNA. To do this, the cell activates pre-replication complexes to make replication origins. These are simply areas of the DNA where replication will begin.

While a simple organism like a single celled protist might only have a single replication origin, more complex organisms have many more. For example, a yeast organism might have up to 400 replication origins while a human cell may have 60,000 replication origins.

Human cells require this huge number of replication origins because human DNA is so long. Scientists know that the DNA replication machinery can only copy about 20 to 100 bases per second, which means a single chromosome would require approximately 2,000 hours to replicate using a single replication origin.

Thanks to the upgrade to 60,000 replication origins, human cells can instead complete S phase in about eight hours.

DNA Synthesis During S Phase

At the replication origin sites, DNA replication relies on an enzyme called helicase. This enzyme unwinds the double-stranded DNA helix – sort of like unzipping a zipper. Once unwound, each of the two strands will become a template to synthesize new strands destined for the daughter cells.

The actual building of the new strands of copied DNA calls for another enzyme, DNA polymerase. The bases (or nucleotides) that comprise the DNA strand must follow the complementary base pairing rule. This requires them to always bind in a specific way: adenine with thymine, and cytosine with guanine. Using this pattern, the enzyme builds a new strand that pairs perfectly with the template.

Just like the original DNA helix, the newly synthesized DNA is very long and requires careful packaging to fit into the nucleus. To do this, the cell produces proteins called histones. These histones act like spools that the DNA wraps around, just like thread on a spindle. Together, the DNA and the histones form complexes called nucleosomes.

DNA Proofreading During S Phase

Of course, it’s vital that the newly synthesized DNA is a perfect match for the template, producing a double-stranded DNA helix identical to the original. Just like you probably do when writing an essay or solving math problems, the cell must check its work to avoid errors.

This is important because the DNA will eventually code for proteins and other important biomolecules. Even a single deleted or changed nucleotide can make the difference between a functional gene product and one that does not work. This DNA damage is one cause of many human diseases.

There are three major checkpoints for proofreading the newly replicated DNA. The first is the replication checkpoint at the replication forks. These forks are simply the places where the DNA unzips and the DNA polymerase builds the new strands.

While adding new bases, the enzyme also checks its work as it moves down the strand. The exonuclease active site on the enzyme can edit out any nucleotides added to the strand in error, preventing mistakes in real time during DNA synthesis.

The other checkpoints – called the S-M checkpoint and the intra-S phase checkpoint – enable the cell to review the newly synthesized DNA for errors that occurred during DNA replication. If errors are found, the cell cycle will pause while kinase enzymes mobilize to the site to repair the errors.

Proofreading Failsafe

Cell cycle checkpoints are crucial for producing healthy, functional cells. Uncorrected errors or damage can cause human diseases, including cancer. If the errors or damage are severe or unrepairable, the cell may undergo apoptosis, or programmed cell death. This essentially kills the cell before it can cause serious problems in your body.