In DNA repair, resection primarily refers to DNA end resection, a fundamental biochemical process crucial for repairing double-stranded DNA (dsDNA) breaks. It's often described as 5′–3′ degradation because it involves the controlled removal of nucleotides from the 5' end of a broken DNA strand.
This process transforms a blunt end of a section of double-stranded DNA by precisely cutting away some nucleotides from the 5' end, thereby producing a 3' single-stranded sequence. This single-stranded DNA is essential for subsequent repair mechanisms.
The Process of DNA End Resection
DNA end resection is a highly regulated step that dictates which repair pathway a cell will utilize for a double-stranded break. Here's how it works:
- Initial State: A double-stranded DNA molecule suffers a break, resulting in two ends. These ends can be "blunt," meaning both strands terminate at the same point.
- Enzymatic Activity: Specific enzymes, primarily nucleases, are recruited to these blunt ends.
- 5′–3′ Degradation: These enzymes meticulously remove nucleotides from the 5' end of each strand. This means the strand running 5' to 3' in one direction is shortened, and the complementary strand (running 3' to 5') is also shortened from its 5' end, progressively extending the 3' overhang.
- Resulting Structure: The outcome is the formation of a single-stranded 3' overhang on both sides of the break. These single-stranded regions are critical for the next stages of DNA repair.
Why Resection is Crucial for DNA Repair
The formation of 3' single-stranded overhangs is not merely a byproduct; it is a deliberate and vital step for several reasons:
- Homologous Recombination (HR): Resection is an absolute prerequisite for the homologous recombination repair pathway. The single-stranded 3' overhangs are necessary for searching for and invading a homologous DNA template (often a sister chromatid) to accurately repair the break. Without these overhangs, HR cannot proceed, potentially leading to errors or reliance on less accurate repair mechanisms.
- Pathway Choice: The extent and timing of DNA end resection are key determinants in the cell's choice between different DNA repair pathways. Extensive resection favors homologous recombination, which is typically error-free as it uses a template. Minimal or no resection allows for Non-Homologous End Joining (NHEJ), a faster but often error-prone repair mechanism that directly ligates broken ends.
- Protection and Loading: The single-stranded DNA created by resection serves as a platform for the loading of repair proteins, such as RPA (Replication Protein A) and Rad51, which further protect the DNA and facilitate the homology search process.
Key Characteristics of DNA End Resection
| Feature | Description |
|---|---|
| Alternative Name | Also known as 5′–3′ degradation. |
| Starting Material | Primarily occurs at the blunt end of a section of double-stranded DNA (dsDNA). |
| Action | Nucleotides are precisely cut away from the 5' end of the broken strands. |
| Result | Production of a 3' single-stranded sequence on both sides of the DNA break. |
| Primary Role | Essential for initiating the homologous recombination (HR) pathway, ensuring high-fidelity DNA repair. |
Practical Insights
Understanding DNA end resection is critical for comprehending how cells maintain genomic integrity. For example, defects in resection machinery can lead to an increased reliance on error-prone repair pathways, contributing to genomic instability, which is a hallmark of many cancers. Research into the enzymes and regulatory factors involved in this process provides potential targets for developing new cancer therapies that exploit vulnerabilities in DNA repair mechanisms.
