single strand break repair

Definition

Target type: biologicalprocess

The repair of single strand breaks in DNA. Repair of such breaks is mediated by the same enzyme systems as are used in base excision repair. [PMID:18626472]

Single-strand break (SSB) repair is a crucial DNA damage repair pathway that safeguards the integrity of the genome by fixing breaks in one strand of the DNA double helix. This repair mechanism is essential for maintaining genomic stability and preventing mutations, which can lead to various diseases, including cancer. SSBs can arise from various sources, including exposure to ionizing radiation, reactive oxygen species, and certain chemicals. The repair process involves the following steps:

1. **Detection and Recognition:** The first step is the recognition of the SSB by specialized DNA repair proteins. These proteins, such as the Mre11-Rad50-NBS1 complex (MRN complex) in eukaryotes, can bind to the broken DNA end and recruit other repair factors to the site.

2. **5’ End Resection:** Once the break is recognized, the 5' end of the broken DNA strand is resected, meaning that nucleotides are removed from the 5' end, creating a 3' single-stranded overhang. This resection is carried out by nucleases, such as the MRN complex and the 5' exonuclease EXO1, which generate the 3' single-stranded tail.

3. **Strand Invasion and DNA Synthesis:** The 3' single-stranded overhang then invades the intact complementary strand of the DNA double helix, forming a displacement loop (D-loop). This process is mediated by the homologous recombination (HR) machinery, which includes proteins like Rad51 and BRCA2. The 3' overhang acts as a primer for DNA polymerase, which uses the intact strand as a template to synthesize a new strand of DNA, filling in the gap created by the SSB.

4. **Ligation:** Once the gap is filled, the newly synthesized DNA strand is joined to the 5' end of the broken strand through a process called ligation. DNA ligases, such as DNA ligase IV, catalyze this step, sealing the nick and restoring the integrity of the DNA double helix.

5. **Error-Free Repair:** The overall process of SSB repair is highly accurate, ensuring that the original sequence is restored without introducing errors. This is due to the use of the complementary strand as a template for DNA synthesis, ensuring that the repair is based on the correct genetic information.

6. **Alternative Pathways:** While the HR-mediated pathway is the primary mechanism for SSB repair, other pathways can also be involved, particularly in cases of specific DNA lesions or in cells lacking certain key HR proteins. For example, base excision repair (BER) and nucleotide excision repair (NER) can also contribute to SSB repair.

SSB repair is a fundamental process for maintaining genome integrity. Defects in this pathway can lead to increased DNA damage, mutations, and genomic instability, ultimately contributing to various diseases and developmental disorders. The complex interplay of proteins and enzymes involved in SSB repair ensures that the damage is efficiently and accurately repaired, preserving the fidelity of the genetic code.'
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Proteins (2)

Compounds (59)