Question

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

Short answer

Answer: DSBR, specifically homologous recombination (HR), mainly occurs during the S and G2 phases since sister chromatids are present for error-free repair. Nonhomologous end joining (NHEJ) predominantly happens during the G1 and early S phase as HR is less active during these periods and serves as an alternative mechanism for repairing double-strand breaks, albeit with a higher chance of mutations.

Step-by-step solution

Understand the cell cycle

The cell cycle consists of four main phases: G1 (Gap 1), S (Synthesis), G2 (Gap 2), and M (Mitosis). During the G1 phase, the cell grows and prepares for DNA replication, which occurs during the S phase. Then, the cell enters the G2 phase, continuing to grow and prepare for mitosis. Finally, mitosis (M phase) includes cell division and replication.

Understand double-strand break repair (DSBR)

Double-strand breaks (DSBs) are DNA damages that can occur during the replication process or due to external factors like radiation. DSBR is a mechanism the cell employs to repair such damages. The two main types of DSBR are homologous recombination (HR) and nonhomologous end joining (NHEJ).

Understand nonhomologous end joining (NHEJ)

Nonhomologous end joining (NHEJ) is a pathway for repairing double-strand breaks in the DNA by directly joining the broken ends without requiring a homologous template. This process may result in the deletion or insertion of base pairs at the damaged site, thereby increasing the chances of mutation.

Identify the cell cycle phases where DSBR and NHEJ occur

DSBR, specifically homologous recombination (HR), mainly occurs during the S and G2 phases since these are the periods when sister chromatids are present, which are used as templates for error-free repair. NHEJ, on the other hand, can happen during any phase of the cell cycle but is more predominant during the G1 and early S phase as HR is less active during these periods.

Explain why DSBR and NHEJ occur in these specific phases

DSBR occurs during the S and G2 phases because these are the phases when sister chromatids are available, allowing the repair machinery to utilize them as templates and ensuring accurate repair of damaged DNA. Since complete and precise DNA repair is crucial for maintaining genomic integrity, the cell prefers error-free repair pathways such as HR during these phases. NHEJ is more predominant during the G1 and early S phase as HR is less active during these periods. In the absence or reduced activity of HR, NHEJ serves as an alternative mechanism for repairing DSBs. However, because NHEJ does not use a homologous template, it may lead to the deletion or insertion of base pairs at the site of damage, making it a more error-prone repair pathway compared to HR.

Key concepts

Double-Strand Break Repair

When the DNA within our cells suffers a severe form of damage known as a double-strand break (DSB), the integrity of our genetic code is compromised. This can be visualized as two back-to-back cuts across the 'twisted ladder' of the DNA double helix. Immediate repair is critical to prevent mutations, cancer, or cell death.

Cells have evolved mechanisms, known collectively as double-strand break repair (DSBR), to address these critical injuries. DSBR can be accurate, using a process called homologous recombination that requires a sister chromatid—a nearly identical copy of the DNA strand—to serve as a template for the repair. However, this method requires the presence of sister chromatids, which are only available after DNA has been replicated in the S phase and before cell division in G2/M phases.

Given the importance of this form of repair, it plays a crucial role in maintaining the genetic stability of our cells, which is vital for healthy cell function and prevention of diseases such as cancer.

Nonhomologous End Joining

A more rough-and-ready approach to handling DSBs is nonhomologous end joining (NHEJ). This repair process does not need a homologous template to fix the break, making it available throughout the cell cycle. NHEJ is crucial because DSBs can happen at any time, and the cell may not always have the luxury of waiting until the DNA replication phase for a template.

In NHEJ, the loose DNA ends are simply detected, brought together, and ligated. This quick fix method can, unfortunately, lead to mistakes such as deletions or insertions of DNA at the break site. While this makes NHEJ potentially mutagenic, its availability throughout the cell cycle makes it an essential backup plan for the cell, especially during the G1 phase when homologous templates are not yet available.

Cell Cycle Phases

Understanding the cell cycle phases is fundamental to appreciating when and how DNA repair processes occur. The cell cycle has four distinct phases: the G1 phase is a period of growth and preparation for DNA replication; the S phase is when DNA replication occurs; the G2 phase is a second period of growth and preparation for division; and the M phase is when the cell divides into two daughter cells.

Each phase has a specific role and conditions which determine the type of DNA repair mechanisms that are most active. For instance, during the G1 phase, the cell is gearing up for DNA replication, which means NHEJ is the repair mechanism on duty. On the other hand, after DNA replication in S phase and before division in G2/M phase, homologous recombination takes the lead in repair processes due to the availability of sister chromatids.

Genomic Integrity

Genomic integrity is the cornerstone of a healthy, functioning cell. It ensures that the genetic information is passed correctly to each daughter cell during division, and it safeguards the cell against transformations that can lead to disease states, such as cancer. Both double-strand break repair mechanisms—homologous recombination and nonhomologous end joining—serve to protect genomic integrity by fixing potentially catastrophic DNA damage.

The choice of repair mechanism is not random but tailored to the cell cycle phase, with the overarching goal of maintaining genomic stability. While homologous recombination is preferred for its accuracy, nonhomologous end joining provides a necessary means to handle DNA damage when a homologous template is unavailable. Consequently, the cell possesses a versatile toolkit for DNA repair, effectively pacing its strategies according to the cell cycle's rhythm and thereby upholding the fidelity of the genome.