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.

Dear Editor,Cancer invasion and metastasis are among the most clinically relevant cancer hallmarks. Identification of molecular pathways that contribute to cancer cell motility a crucial step in cancer invasion/metastasis is essential to understanding how cancer motility is regulated and may provide therapeutic targets for treating metastatic cancer. Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1) is a novel oncoprotein whose high-leveled expressions have been correlated with advanced and metastatic stages of cancer [1-3]. We have previously uncovered BAIAP2L1 as a novel oncogene by integrative analysis of protein-protein interactome and somatic copy number alterations in human cancers [4]. Although in vivo xenograft model showed that BAIAP2L1 promoted tumor growth [4], however, the exact mechanism by which BAIAP2L1 facilitates tumorigenesis remains unclear.We hypothesized that expressions of BAIAP2L1 were involved with metastatic/invasive phenotypes of cancer. To investigate, we selected the breast cancer cell line MCF7 which expressed an acceptable level of BAIAP2L1 mRNA (Supplementary Fig. S1). Detailed methods can be found in the Supplementary File. We depleted endogenous BAIAP2L1 in MCF7 by BAIAP2L1-specific shorthairpin RNAs (shRNAs) and measured cancer cell migration via wound-healing assay. We found that BAIAP2L1-