Question

In which phases of the cell cycle would you expect double-strand break repair and nonhomologous end joining to occur and why?

Short answer

Answer: Double-strand break repair (DSBR) can occur throughout the cell cycle, but different mechanisms are more prevalent in specific phases. Homologous recombination (HR), a high-fidelity repair mechanism, is more likely to occur during the late S and G2 phases when sister chromatids are available. In contrast, nonhomologous end joining (NHEJ), a more error-prone repair mechanism, is expected to be more prevalent during the G1 phase, although it can also occur during the S and G2 phases.

Step-by-step solution

Introduction to the Cell Cycle

The cell cycle consists of four main phases: G1, S, G2, and M. During G1, the cell prepares for DNA replication by synthesizing proteins and other necessary components. The S phase is when the DNA is replicated, resulting in two identical sister chromatids. In the G2 phase, the cell continues to grow and prepares for mitosis (cell division). Finally, the M phase is when the cell divides its DNA and cytoplasm, resulting in two daughter cells.

Double-Strand Break Repair

Double-strand break repair (DSBR) is a DNA repair mechanism that corrects double-strand breaks in DNA. These breaks can be caused by various factors, including exposure to ionizing radiation, chemical agents, or errors during DNA replication. DSBR occurs in two main pathways: homologous recombination (HR) and nonhomologous end joining (NHEJ). HR uses an undamaged sister chromatid as a template to repair the broken DNA, whereas NHEJ simply joins the broken ends together without the need for a template.

Homologous Recombination

Homologous recombination (HR) is a high-fidelity repair mechanism that requires the presence of an undamaged sister chromatid as a template. This means that HR is most likely to occur during the late S and G2 phases of the cell cycle when sister chromatids are available. HR is less likely to occur during the G1 phase because there are no sister chromatids present, and the DNA has not yet been replicated.

Nonhomologous End Joining

Nonhomologous end joining (NHEJ) is a more error-prone repair mechanism that can occur throughout the cell cycle. NHEJ does not require the presence of a sister chromatid, so it can take place during the G1, S, or G2 phases. However, it is thought to be more prevalent during the G1 phase because HR, a more accurate repair mechanism, is not available at this time. It is also possible for NHEJ to occur during the late S and G2 phases but is generally considered less likely in favor of HR.

Conclusion

In summary, double-strand break repair is expected to occur throughout the cell cycle, but different mechanisms are more predominant in different phases. Homologous recombination, a high-fidelity repair mechanism, is more likely to occur during the late S and G2 phases. In contrast, nonhomologous end joining, a more error-prone repair mechanism, is expected to be more prevalent during the G1 phase, although it can also occur during the S and G2 phases.

Key concepts

Double-strand Break Repair

When the integrity of our DNA is compromised due to double-strand breaks (DSBs), the cell deploys critical repair mechanisms to prevent genetic instability and disease. Think of DSBs as severe injuries within the DNA double helix, potentially catastrophic if left unrepaired. They can occur from both exogenous sources such as ionizing radiation and endogenous processes like oxidative stress. Cells tackle these breaks through a process known as double-strand break repair.

This repair is akin to emergency surgery for the cell, a procedure that must be accurate to maintain the cell's genomic integrity. Failure to correctly repair DSBs can lead to mutations, which may cause cancer or cell death. Double-strand break repair is thus a pivotal aspect of cellular health and longevity.

Nonhomologous End Joining

In the event of a double-strand break, nonhomologous end joining (NHEJ) is often the first on the scene. It’s the cellular equivalent of patching up a wound without the need for a perfect match between the broken ends - a kind of 'quick fix'. NHEJ doesn’t fuss over details; it's a mechanism that can function at any point in the cell cycle, making it the more versatile repair option.

Unlike its more meticulous counterpart, homologous recombination, NHEJ doesn't need a template to repair the break. It just bridges the gap directly, regardless of the cell cycle phase. However, this convenience comes at a cost; NHEJ is prone to errors and often results in small deletions or insertions at the repair site. For this reason, it's a vital yet potentially risky way to keep the genetic workflow moving without causing excessive downtime for the cell.

Homologous Recombination

Homologous recombination (HR) is the more meticulous and precise sibling in the DNA repair family. It takes a mindful approach to mending double-strand breaks by using an identical or nearly identical piece of DNA as a template, typically from the sister chromatid. It's like using a reference manual to ensure the repair is executed flawlessly.

This process is more common when sister chromatids are present, which is during and after DNA replication - in the late S and G2 phases of the cell cycle. Given its dependence on a homologous sequence, HR is a high-fidelity repair mechanism, greatly reducing the chance of errors and maintaining genetic integrity.

Phases of the Cell Cycle

The cell cycle is an ordered series of events that leads to cell proliferation. It's like the life cycle of a cell, starting with its birth and ending with its division into two daughter cells. The key phases are G1 (the cell grows and prepares for DNA replication), S (the cell copies its DNA), G2 (additional growth and preparation for division), and M (mitosis, where the cell splits itself into two separate cells).

Understanding the cell cycle is crucial for comprehending when and how double-strand break repair mechanisms operate. For instance, nonhomologous end joining, which does not need a sister chromatid, can act at any stage, particularly in G1. In contrast, homologous recombination, requiring a template, is reserved for the late S and G2 phases. It's a choreographed dance ensuring that cells maintain their genetic code intact as they replicate and divide.