Mus81-KO Mouse

Mus81, the methyl methanesulfonate and UV-sensitive protein 81, is an important structure-specific endonuclease. It functions in DNA repair, especially in processing stalled replication forks and recombination intermediates. Mus81 forms complexes with regulatory subunits like EME1 and EME2, and is involved in pathways related to DNA replication, recombination, and cell cycle regulation [3,5]. Its activity is crucial for ensuring proper chromosome segregation during the cell cycle [3].

Research has shown that MUS81 is dispensable for embryonic development and cell viability in mammals [1]. In rice, mutation analysis indicates that MUS81 contributes little to crossover designation but is crucial for resolving atypical meiotic intermediates [4]. In human cells, studies suggest that MUS81 can cleave TOP1-derived lesions and other DNA-protein cross-links, and it has an independent role with TDP1 in repairing CPT-induced lesions, making it a potential therapeutic target for cancer cell sensitization [2]. In gastric cancer, knockdown of MUS81 enhances the anticancer effect of the PARP inhibitor talazoparib by impairing the ATR/CHK1 cell cycle signaling pathway [6].

In conclusion, Mus81 plays essential roles in DNA repair, replication, and recombination processes. Its study through gene knockout models in various organisms has provided insights into its functions in different biological processes and disease conditions, especially in cancer. Understanding Mus81's functions offers potential therapeutic strategies for cancer treatment, highlighting its significance in biomedical research.

References:

1. Chen, Sisi, Geng, Xinwei, Syeda, Madiha Zahra, Zhang, Chao, Ying, Songmin. 2021. Human MUS81: A Fence-Sitter in Cancer. In Frontiers in cell and developmental biology, 9, 657305. doi:10.3389/fcell.2021.657305. https://pubmed.ncbi.nlm.nih.gov/33791310/

2. Marini, Victoria, Nikulenkov, Fedor, Samadder, Pounami, Knudsen, Birgitta R, Krejci, Lumir. 2023. MUS81 cleaves TOP1-derived lesions and other DNA-protein cross-links. In BMC biology, 21, 110. doi:10.1186/s12915-023-01614-1. https://pubmed.ncbi.nlm.nih.gov/37194054/

3. Pfander, Boris, Matos, Joao. 2017. Control of Mus81 nuclease during the cell cycle. In FEBS letters, 591, 2048-2056. doi:10.1002/1873-3468.12727. https://pubmed.ncbi.nlm.nih.gov/28640495/

4. Mu, Na, Li, Yafei, Li, Sanhe, You, Aiqing, Cheng, Zhukuan. 2022. MUS81 is required for atypical recombination intermediate resolution but not crossover designation in rice. In The New phytologist, 237, 2422-2434. doi:10.1111/nph.18668. https://pubmed.ncbi.nlm.nih.gov/36495065/

5. Hua, Zhengkang, Fang, Qianqian, Zhang, Danping, Yuan, Cai, Lin, Zhonghui. 2022. Crystal structure of the human MUS81-EME2 complex. In Structure (London, England : 1993), 30, 743-752.e3. doi:10.1016/j.str.2022.02.015. https://pubmed.ncbi.nlm.nih.gov/35290797/

6. Wang, Tao, Zhang, Peng, Li, Chengguo, Tao, Kaixiong, Yin, Yuping. 2022. MUS81 Inhibition Enhances the Anticancer Efficacy of Talazoparib by Impairing ATR/CHK1 Signaling Pathway in Gastric Cancer. In Frontiers in oncology, 12, 844135. doi:10.3389/fonc.2022.844135. https://pubmed.ncbi.nlm.nih.gov/35480096/