double-strand break repair via synthesis-dependent strand annealing

Definition

Target type: biologicalprocess

SDSA is a major mechanism of double-strand break repair in mitosis which allows for the error-free repair of a double-strand break without the exchange of adjacent sequences. The broken DNA searches for and base pairs with a homologous region in an intact chromosome. DNA synthesis initiates from the 3' end of the invading DNA strand, using the intact chromosome as the template. Newly synthesized DNA is then displaced from the template and anneal with its complement on the other side of the double-strand break. [PMID:10357855]

Synthesis-dependent strand annealing (SDSA) is a crucial double-strand break (DSB) repair pathway in eukaryotic cells. It involves the following steps:

1. **DSB Recognition and Processing:**
* Upon a DSB, the MRN complex (Mre11, Rad50, and Nbs1) recognizes the break site.
* The MRN complex recruits the ATM kinase, which activates the DNA damage response (DDR).
* The 5' end of the break is resected by the exonuclease activity of MRN and CtIP, generating 3' single-stranded DNA tails.

2. **Strand Invasion and Replication Fork Formation:**
* The 3' tail invades the homologous chromosome, facilitated by the RAD51 recombinase.
* RAD51 forms a nucleoprotein filament on the single-stranded tail, promoting homology search and strand invasion.
* The invading strand displaces the corresponding strand on the homologous chromosome, forming a D-loop structure.

3. **DNA Synthesis and Displacement Loop Formation:**
* DNA polymerase uses the homologous chromosome as a template to synthesize new DNA, extending the invading strand.
* The newly synthesized DNA forms a displacement loop (D-loop) by displacing the homologous strand.

4. **Strand Annealing and Break Resolution:**
* The newly synthesized DNA on the invading strand anneals to the complementary strand of the broken DNA molecule.
* The D-loop is dissolved, and the remaining single-stranded gap is filled by DNA polymerase.

5. **Ligase-Mediated Joining:**
* The final step involves the ligation of the newly synthesized DNA to the broken DNA molecule by DNA ligase.

SDSA repair is characterized by its high fidelity, as it relies on homologous recombination for accurate repair. It plays a crucial role in maintaining genomic integrity, protecting against mutations, and ensuring proper cell function.
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