Single-strand Breaks

Definition

Single-strand breaks (SSBs) are a type of DNA damage that occurs when the phosphodiester backbone of one strand of the DNA double helix is severed, leaving the complementary strand intact. This disruption in the DNA structure can have significant implications for cellular function and viability, particularly in the context of ionizing radiation exposure.

5 Must Know Facts For Your Next Test

1. Single-strand breaks can be caused by various factors, including oxidative stress, ionizing radiation, and certain chemotherapeutic agents.
2. SSBs can lead to the stalling or collapse of replication forks, which can result in the formation of more severe DNA lesions, such as double-strand breaks.
3. The repair of single-strand breaks is primarily mediated by the base excision repair (BER) pathway, which involves the recognition and removal of the damaged DNA segment, followed by the restoration of the correct nucleotide sequence.
4. Unrepaired or misrepaired single-strand breaks can contribute to genomic instability, which is a hallmark of cancer and other diseases.
5. The presence of single-strand breaks can also trigger cellular stress responses, such as the activation of cell cycle checkpoints and the induction of apoptosis (programmed cell death).

Review Questions

• Explain how single-strand breaks differ from double-strand breaks in terms of their impact on cellular function and DNA repair mechanisms.
  • Single-strand breaks (SSBs) and double-strand breaks (DSBs) differ in their severity and the cellular responses they elicit. SSBs involve the severing of one strand of the DNA double helix, leaving the complementary strand intact. This type of damage is generally less severe than DSBs, where both strands of the DNA are severed. While SSBs can lead to the stalling or collapse of replication forks, they are typically repaired more efficiently by the base excision repair (BER) pathway. In contrast, DSBs pose a greater threat to genomic integrity and are repaired by more complex mechanisms, such as non-homologous end joining and homologous recombination. The presence of unrepaired or misrepaired DSBs is more likely to contribute to genomic instability and the development of diseases like cancer.
• Describe the role of ionizing radiation in the formation of single-strand breaks and the cellular consequences of this type of DNA damage.
  • Ionizing radiation is a significant contributor to the formation of single-strand breaks (SSBs) in DNA. This high-energy radiation can directly or indirectly cause the severing of the phosphodiester backbone of one strand of the DNA double helix. The presence of SSBs can lead to the stalling or collapse of replication forks, which can in turn result in the formation of more severe DNA lesions, such as double-strand breaks. Unrepaired or misrepaired SSBs can also contribute to genomic instability, a hallmark of cancer and other diseases. Cellular responses to SSBs induced by ionizing radiation include the activation of cell cycle checkpoints and the induction of apoptosis, as the cell attempts to maintain genomic integrity or eliminate severely damaged cells. Understanding the role of ionizing radiation in the formation of SSBs and the subsequent cellular consequences is crucial for understanding the biological effects of this type of radiation exposure.
• Analyze the significance of the base excision repair (BER) pathway in the context of single-strand breaks and its implications for cellular function and disease prevention.
  • The base excision repair (BER) pathway plays a critical role in the repair of single-strand breaks (SSBs) and other types of DNA damage involving modified bases, such as oxidation or alkylation. This repair mechanism is essential for maintaining genomic integrity and preventing the accumulation of unrepaired or misrepaired SSBs, which can contribute to genomic instability and the development of diseases like cancer. By recognizing and removing the damaged DNA segment, and then restoring the correct nucleotide sequence, the BER pathway helps to mitigate the cellular consequences of SSBs, including the stalling or collapse of replication forks and the activation of cellular stress responses. The efficiency and fidelity of the BER pathway are crucial for ensuring the proper functioning of cellular processes and preventing the propagation of genetic errors that could lead to disease. Understanding the importance of the BER pathway in the context of SSB repair is essential for developing targeted therapies and preventive strategies for conditions associated with DNA damage and genomic instability.

Related terms

Double-strand Breaks: Double-strand breaks (DSBs) occur when both strands of the DNA double helix are severed, leading to a more severe form of DNA damage compared to single-strand breaks.

Base Excision Repair: Base excision repair (BER) is a DNA repair pathway that specifically addresses single-strand breaks and other types of DNA damage involving modified bases, such as oxidation or alkylation.

Ionizing Radiation: Ionizing radiation is a type of high-energy radiation that can directly or indirectly cause the formation of single-strand breaks and other types of DNA damage.