A DNA repair player, ring finger protein 43, relieves etoposide‐induced topoisomerase II poisoning. (19th October 2020)

• Record Type: Journal Article
• Authors: Lerksuthirat, Tassanee; Wikiniyadhanee, Rakkreat; Stitchantrakul, Wasana; Chitphuk, Sermsiri; Stansook, Nauljun; Pipatpanyanugoon, Nut; Jirawatnotai, Siwanon; Dejsuphong, Donniphat
• Is Part Of: Genes to cells. Volume 25:Number 11(2020)
• Page Start: 718
• Page End: 729
• Publication Date: 2020-10-19
• Subjects: DNA damage and repair -- DNA double‐strand break -- DT40 -- etoposide -- RNF43 -- Topoisomerase II; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12808
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: Ring finger protein 43 (RNF43) is an E3 ubiquitin ligase which is well‐known for its role in negative regulation of the Wnt‐signaling pathway. However, the function in DNA double‐strand break repairs has not been investigated. In this study, we used a lymphoblast cell line, DT40, and mouse embryonic fibroblast as cellular models to study DNA double‐strand break (DSB) repairs. For this purpose, we created RNF43 knockout, RNF43 −/− DT40 cell line to investigate DSB repairs. We found that deletion of RNF43 does not interfere with cell proliferation. However, after exposure to various types of DNA‐damaging agents, RNF43 −/− cells become more sensitive to topoisomerase II inhibitors, etoposide, and ICRF193, than wild type cells. Our results also showed that depletion of RNF43 results in apoptosis upon etoposide‐mediated DNA damage. The delay in resolution of γH2AX and 53BP1 foci formation after etoposide treatment, as well as epistasis analysis with DNAPKcs, suggested that RNF43 might participate in DNA repair of etoposide‐induced DSB via non‐homologous end joining. Disturbed γH2AX foci formation in MEFs following pulse etoposide treatment supported the notion that RNF43 also functions DNA repair in mammalian cells. These findings propose two possible functions of RNF43, either participating in NHEJ or removing the blockage of 5′ topo II adducts from DSB ends. Abstract : Identification of RNF43 function in DNA repair induced by etoposide, either through participating in NHEJ or removing the blockage of 5' topo‐II adducts from DSB ends.