Rad52-KO Mouse

RAD52, also known as Mammalian Radiation Sensitive 52, is a key gene involved in multiple DNA metabolic pathways. It plays a significant role in homologous recombination (HR), a high-fidelity pathway for repairing double-stranded DNA damage. RAD52 also participates in processes like break-induced replication (BIR), single-strand annealing, and RNA-mediated repair of DNA, which are crucial for maintaining genome stability [1].

Although RAD52 was once thought dispensable in mammals due to lack of discernable phenotypes in knockout mice, recent studies have shown its importance. In HR-deficient cancer cells, RAD52 is critical for backup DNA repair pathways. For example, inactivation of RAD52 in BRCA1-or BRCA2-defective cells is synthetically lethal, highlighting its potential as a therapeutic target for homologous-recombination-deficient cancers [1,3,4,5]. Also, RAD52 deficiency increases R-loop accumulation, exacerbating transcription-replication conflicts and leading to elevated DNA damage, indicating its role in maintaining genome stability [2].

In conclusion, RAD52 is essential for DNA repair and genome maintenance. Its functions are especially crucial in HR-deficient cancer cells, making it an attractive target for anti-cancer therapies. The study of RAD52 using knockout mouse models has revealed its significance in various DNA-related biological processes and disease conditions, particularly in the context of cancer [1,3,4,5].

References:

1. Rossi, Matthew J, DiDomenico, Sarah F, Patel, Mikir, Mazin, Alexander V. 2021. RAD52: Paradigm of Synthetic Lethality and New Developments. In Frontiers in genetics, 12, 780293. doi:10.3389/fgene.2021.780293. https://pubmed.ncbi.nlm.nih.gov/34887904/

2. Jalan, Manisha, Sharma, Aman, Pei, Xin, Riaz, Nadeem, Powell, Simon N. 2024. RAD52 resolves transcription-replication conflicts to mitigate R-loop induced genome instability. In Nature communications, 15, 7776. doi:10.1038/s41467-024-51784-x. https://pubmed.ncbi.nlm.nih.gov/39237529/

3. Liang, Chih-Chao, Greenhough, Luke A, Masino, Laura, Taylor, Ian A, West, Stephen C. 2024. Mechanism of single-stranded DNA annealing by RAD52-RPA complex. In Nature, 629, 697-703. doi:10.1038/s41586-024-07347-7. https://pubmed.ncbi.nlm.nih.gov/38658755/

4. Jalan, Manisha, Olsen, Kyrie S, Powell, Simon N. 2019. Emerging Roles of RAD52 in Genome Maintenance. In Cancers, 11, . doi:10.3390/cancers11071038. https://pubmed.ncbi.nlm.nih.gov/31340507/

5. Wu, Xiaohua. 2019. Replication Stress Response Links RAD52 to Protecting Common Fragile Sites. In Cancers, 11, . doi:10.3390/cancers11101467. https://pubmed.ncbi.nlm.nih.gov/31569559/

6. Balboni, Beatrice, Rinaldi, Francesco, Previtali, Viola, Girotto, Stefania, Cavalli, Andrea. 2023. Novel Insights into RAD52's Structure, Function, and Druggability for Synthetic Lethality and Innovative Anticancer Therapies. In Cancers, 15, . doi:10.3390/cancers15061817. https://pubmed.ncbi.nlm.nih.gov/36980703/