SWSAP1: An Essential Factor Required for Efficient Homologous Recombination Repair

SWS1-Associated Protein 1 (SWSAP1) is a protein that plays a key role in homologous recombination (HR) repair, especially in the repair of DNA double-strand breaks (DSBs). It forms a complex with the SWS1 protein (hSWS1·SWSAP1) and participates in maintaining genome stability. In cells, the repair of DNA damage is a key process to maintain genome stability and cell health, and homologous recombination is one of the most important mechanisms to repair double-strand breaks (DSBs).

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SWSAP1 Plays a Key Role in Homologous Recombination Repair

The DNA repair mechanism called homology-directed repair (HDR) has high fidelity and is designated for repairing DNA double-strand breaks (DSBs). The DNA repair mechanism depends on a template DNA that shows high homological similarity. The HDR process functions as a crucial DNA repair system to uphold genome stability during the S and G2 phases of the cell cycle. The HDR pathway serves as a crucial mechanism for DNA repair in mammalian cells. The repair system operates through a complex mechanism that produces various outcomes which impact genome integrity differently.

Promote DNA End Processing

SWSAP1 can help process broken ends after DNA damage occurs, providing suitable substrates for subsequent homologous recombination.

Synergistic Effect

SWSAP1 interacts with other DNA repair factors (such as RAD51) to help assemble repair complexes, thereby enhancing the efficiency of homologous recombination.

Affecting Chromosome Stability

By regulating the process of homologous recombination, SWSAP1 can maintain the chromosome stability of cells and prevent diseases caused by potential genomic instability, such as cancer.

Regulating the Choice of Repair Pathways

Different types of DNA damage conditions prompt SWSAP1 to regulate whether cells use homologous recombination or alternative repair mechanisms like non-homologous end joining. During homologous recombination repair SWSAP1 plays an essential role as it helps identify DNA damage and processes DNA ends while forming repair complexes. Researchers focus on it when studying DNA repair processes and associated diseases.

Functions of SWSAP1

Promote the Function of RAD51

The primary protein RAD51 engages in homologous recombination repair by identifying matching sequences at broken DNA ends and triggering strand exchange. SWSAP1 functions as a RAD51 loading factor as well as a stabilizing factor.

Forming a Complex with hSWS1

The formation of a stable complex between SWSAP1 and SWS1 strengthens SWS1's function during DNA repair operations. SWSAP1 functions in concert with additional HR-related proteins including BRCA2 and FIGNL1.

Inhibition of Anti-recombination Factors

The protein SWSAP1 blocks the action of RAD51 depolymerization factor FIGNL1 to maintain RAD51-DNA nucleosome stability.

Fig 1. Human SWS1, SWSAP1, and SPIDR interact and participate in important homology-directed repair (HDR) activities (Prakash, R., et al. 2021).

Consequences of SWSAP1 Deficiency

If SWSAP1 is missing in cells, the following serious consequences will occur:

• Decrease in homologous recombination repair efficiency: RAD51 cannot be effectively loaded into the DNA damage site, resulting in a significant decrease in HR repair efficiency. The repair process is blocked, increasing DNA damage accumulation.
• Increased genomic instability: DNA double-strand breaks cannot be repaired normally, resulting in chromosome aberrations, breaks, fusions, etc. Long-term effects may cause genomic instability-related diseases such as cancer.
• Cells are more sensitive to DNA damage: Cells lacking SWSAP1 are more sensitive to DNA damaging agents (such as ultraviolet rays, mitomycin, cisplatin, etc.). Cell cycle arrest and even induction of programmed cell death (apoptosis).
• Embryonic development defects: In mouse models, SWSAP1 deficiency can lead to embryonic lethality or severe developmental abnormalities.

References

1. Prakash, R., et al. Distinct pathways of homologous recombination controlled by the SWS1–SWSAP1–SPIDR complex. Nature communications. 2021, 12(1): 4255.
2. Liu, T., et al. hSWS1· SWSAP1 is an evolutionarily conserved complex required for efficient homologous recombination repair. Journal of Biological Chemistry. 2011, 286(48): 41758-41766.