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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Ubiquitin E3 ligases in cancer: somatic mutation and amplification

  • Eun-Hye Jo (Department of Biological Sciences and Technology, Chonnam National University) ;
  • Mi-Yeon Kim (Department of Biological Sciences and Technology, Chonnam National University) ;
  • Hyung-Ju Lee (Department of Biological Sciences and Technology, Chonnam National University) ;
  • Hee-Sae Park (Department of Biological Sciences and Technology, Chonnam National University)
  • Received : 2023.02.24
  • Accepted : 2023.04.20
  • Published : 2023.05.31
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Abstract

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. NRF-2022R1H1A2091883, NRF2019R1A2C1007197).

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