positive regulation of double-strand break repair via homologous recombination

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of double-strand break repair via homologous recombination. [GO_REF:0000058, GOC:TermGenie, PMID:12023299]

Positive regulation of double-strand break repair via homologous recombination is a critical cellular process that ensures the accurate repair of DNA double-strand breaks (DSBs), preserving genomic integrity. This intricate process involves several key steps:

1. **DSB Sensing and End Resection:** Upon a DSB, the MRN complex (Mre11-Rad50-Nbs1) recognizes the break and initiates end resection, a process that degrades 5' ends of the broken DNA strand to create 3' single-stranded DNA (ssDNA) tails.

2. **Recruitment of Recombinase:** The ssDNA tails are coated with Replication Protein A (RPA), which recruits the recombinase Rad51. Rad51 forms filaments on the ssDNA, promoting strand invasion into the homologous chromosome.

3. **Strand Invasion and Homologous Pairing:** The Rad51-coated ssDNA searches for homology within the sister chromatid or a homologous chromosome. When homology is found, the 3' end of the broken strand invades the intact DNA duplex, forming a displacement loop (D-loop).

4. **DNA Synthesis and Ligase Activity:** The invading strand serves as a primer for DNA polymerase, which synthesizes a new DNA strand using the intact homologous chromosome as a template. This process extends the invading strand and fills the gap in the broken DNA molecule.

5. **Resolution and Repair:** The newly synthesized DNA is ligated to the broken strand, creating a complete and repaired DNA molecule. This process usually involves a second homologous recombination event to ensure accurate repair.

The positive regulation of this pathway ensures that the process proceeds efficiently and accurately, minimizing errors and preventing detrimental mutations. This regulation occurs at multiple levels:

* **Transcriptional Regulation:** Genes encoding key proteins in the pathway, such as Rad51, are transcriptionally regulated by DNA damage signals.
* **Post-translational Modifications:** Proteins involved in the pathway undergo various post-translational modifications, including phosphorylation, ubiquitination, and acetylation. These modifications influence protein stability, activity, and localization.
* **Protein Interactions:** Complex protein interactions regulate the recruitment and activation of key proteins, ensuring their proper function within the pathway.

Overall, positive regulation of homologous recombination repair is crucial for maintaining genome stability and preventing disease. Dysregulation of this pathway can lead to genomic instability and contribute to various diseases, including cancer.'
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Proteins (11)

Compounds (317)