Msh2-KO Mouse

Msh2, or MutS homolog 2, is a crucial gene involved in DNA mismatch repair (MMR) pathways. The proteins encoded by Msh2 are essential for MMR, maintaining genome stability by correcting replication errors. This function is vital in preventing cancer development, as MMR deficiency can lead to increased mutation frequencies and cancer cell resistance to chemotherapy [1,5].

In Arabidopsis, Msh2 has been shown to be a master regulator of meiotic DSB repair. It stimulates interfering crossovers while inhibiting non-interfering crossovers in response to genetic polymorphism, thus shaping the crossover landscape in relation to interhomolog polymorphism [2]. In yeast, elevated Msh2-Msh3 levels (where Msh2 is a subunit) interfere with DNA replication and base excision repair in vivo, highlighting the role of Msh2-Msh3 protein abundance in Msh2-Msh3-mediated genomic instability [3]. In bladder cancer, Msh2 acts as a mediator of cisplatin sensitivity, and its interaction with circLIFR positively modulates sensitivity to cisplatin both in vitro and in vivo [4].

In summary, Msh2 is essential for DNA mismatch repair, playing a key role in maintaining genome stability. Studies in different organisms and disease models, such as Arabidopsis, yeast, and bladder cancer, have revealed its significance in various biological processes and disease conditions. These findings contribute to understanding the mechanisms underlying genome stability and cancer development, potentially providing insights for cancer treatment strategies [1-4,7].

References:

1. Bouvet, Delphine, Bodo, Sahra, Munier, Annie, Coulet, Florence, Muleris, Martine. 2019. Methylation Tolerance-Based Functional Assay to Assess Variants of Unknown Significance in the MLH1 and MSH2 Genes and Identify Patients With Lynch Syndrome. In Gastroenterology, 157, 421-431. doi:10.1053/j.gastro.2019.03.071. https://pubmed.ncbi.nlm.nih.gov/30998989/

2. Dluzewska, Julia, Dziegielewski, Wojciech, Szymanska-Lejman, Maja, Higgins, James D, Ziolkowski, Piotr A. 2023. MSH2 stimulates interfering and inhibits non-interfering crossovers in response to genetic polymorphism. In Nature communications, 14, 6716. doi:10.1038/s41467-023-42511-z. https://pubmed.ncbi.nlm.nih.gov/37872134/

3. Medina-Rivera, Melisa, Phelps, Samantha, Sridharan, Madhumita, Balakrishnan, Lata, Surtees, Jennifer A. . Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo. In Nucleic acids research, 51, 12185-12206. doi:10.1093/nar/gkad934. https://pubmed.ncbi.nlm.nih.gov/37930834/

4. Zhang, Hui, Xiao, Xingyuan, Wei, Wenjie, Jiang, Guosong, Zhang, Xiaoping. 2021. CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer. In Molecular cancer, 20, 70. doi:10.1186/s12943-021-01360-4. https://pubmed.ncbi.nlm.nih.gov/33874956/

5. Wu, Qiong, Huang, Yaping, Gu, Liya, Chang, Zhijie, Li, Guo-Min. 2021. OTUB1 stabilizes mismatch repair protein MSH2 by blocking ubiquitination. In The Journal of biological chemistry, 296, 100466. doi:10.1016/j.jbc.2021.100466. https://pubmed.ncbi.nlm.nih.gov/33640455/