The role of protein arginine methylation 5 in DNA damage repair and cancer therapy
Qikun Gao , Ziyi Liu , Jinyang Liu , Xuyang Yan , Junfei Dai , Zixuan Zhang , Rongxiao Li , Shiva Basnet , Changzheng Du
Genome Instability & Disease ›› 2023, Vol. 4 ›› Issue (6) : 305 -314.
Protein arginine methylation, a post-translational modification (PTM), is fundamental in regulating protein function and stability. Among the nine protein methyl transferases (PRMT), PRMT5 plays a critical role in promoting oncogenic processes including tumor proliferation, invasiveness, immune escape and DNA damage repair through different signaling pathways. It is also a target in cancer therapy, with numerous inhibitors in clinical trial. In this review, we focus on the biological functions of PRMT5 in DNA damage repair and maintenance of genome stability in cancer, and summarize the development advance of PRMT5 inhibitors in cancer therapy.
PRMT5 / DNA damage repair / Genome stability
| [1] |
|
| [2] |
|
| [3] |
Clarke, T.L/, Sanchez-Bailon. M.P., Chiang, K., Reynolds, J.J., Herrero-Ruiz, J., Bandeiras, T.M., Matias, P.M., Maslen, S.L., Skehel, J.M., Stewart, G.S., Davies C.C. (2017). PRMT5-Dependent methylation of the TIP60 coactivator RUVBL1 is a key regulator of homologous recombination. Mol Cell, 65(5): 900–916 e907. |
| [4] |
Du, C., Hansen, L.J., Singh, S.X., Wang, F., Sun, R., Moure, C.J., Roso, K., Greer. P.K., Yan, H., He, Y. (2019). A PRMT5-RNF168-SMURF2 axis controls H2AX proteostasis. Cell Reports, 28(12): 3199–3211 e3195. |
| [5] |
|
| [6] |
|
| [7] |
|
| [8] |
|
| [9] |
|
| [10] |
|
| [11] |
|
| [12] |
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
Motolani, A., Martin, M., Sun, M., Lu, T. (2021). The structure and functions of PRMT5 in human diseases. Life (Basel), 11(10). |
| [20] |
Musiani, D., Bok, J., Massignani, E., Wu, L., Tabaglio, T., Ippolito, M.R., Cuomo, A., Ozbek, U., Zorgati. H., Ghoshdastider, U., Robinson, R.C., Guccione, E., Bonaldi, T. (2019). Proteomics profiling of arginine methylation defines PRMT5 substrate specificity. Sci Signal, 12(575). |
| [21] |
Owens, J.L., Beketova, E., Liu, S., Tinsley, S.L., Asberry, A.M., Deng, X., Huang, J., Li, C., Wan, J., Hu, C.D. (2020). PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes. iScience, 23(1): 100750. |
| [22] |
|
| [23] |
|
| [24] |
|
| [25] |
|
| [26] |
Tan DQ, Li Y, Yang C, Li J, Tan SH, Chin DWL, Nakamura-Ishizu A, Yang H, Suda T. (2019) PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells. Cell Reports, 26(9): 2316–2328 e2316. |
| [27] |
|
| [28] |
|
| [29] |
|
| [30] |
|
/
| 〈 |
|
〉 |