DNA damage often occurs in the S phase of the eukaryotic cell cycle. Explain why this is the case.

The S phase, or synthesis phase, of the eukaryotic cell cycle is when DNA replication occurs. This process involves unwinding the DNA double helix and using each strand as a template to synthesize a new complementary strand.

1. Unwinding and Separation: The first step in DNA replication is the unwinding and separation of the double helix by the enzyme helicase. This creates a 'replication fork' - a Y-shaped structure where the DNA is being unwound and separated into two single strands.

2. Primer Binding: The next step is the binding of RNA primers to the separated strands of DNA by the enzyme primase. These primers serve as a starting point for the synthesis of the new DNA strands.

3. Elongation: The enzyme DNA polymerase then adds new nucleotides to the RNA primer, building a new strand of DNA. This process is continuous on the leading strand and discontinuous on the lagging strand, creating Okazaki fragments.

4. Termination: Once the entire DNA molecule has been replicated, the RNA primers are removed and replaced with DNA by the enzyme DNA polymerase. The Okazaki fragments on the lagging strand are then joined together by the enzyme DNA ligase to create a continuous DNA strand.

Because the DNA is being unwound and separated, and new strands are being synthesized, there is a high potential for errors to occur during the S phase. These errors can lead to DNA damage. For example, if the DNA polymerase makes a mistake and adds the wrong nucleotide, this can lead to a mutation in the DNA sequence. Additionally, the process of unwinding the DNA can lead to the formation of supercoils, which can cause physical damage to the DNA molecule. Therefore, the S phase of the cell cycle is a critical period for DNA damage to occur.