1. Academic Validation
  2. Genistein-induced DNA damage is repaired by nonhomologous end joining and homologous recombination in TK6 cells

Genistein-induced DNA damage is repaired by nonhomologous end joining and homologous recombination in TK6 cells

  • J Cell Physiol. 2019 Mar;234(3):2683-2692. doi: 10.1002/jcp.27082.
Xiaoqing Hu 1 Xiaohua Wu 1 Hao Liu 1 Ziyuan Cheng 1 Zilu Zhao 1 Cuifang Xiang 1 Xiaoyu Feng 1 Shunichi Takeda 2 Yong Qing 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy, West China Hospital, and Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
  • 2 Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Abstract

Genistein (GES), a phytoestrogen, has potential chemopreventive and chemotherapeutic effects on Cancer. The Anticancer mechanism of GES may be related with Topoisomerase II associated DNA double-strand breaks (DSBs). However, the precise molecular mechanism remains elusive. Here, we performed genetic analyses using human lymphoblastoid TK6 cell lines to investigate whether non-homologous DNA end joining (NHEJ) and homologous recombination (HR), the two major repair pathways of DSBs, were involved in repairing GES-induced DNA damage. Our results showed that GES induced DSBs in TK6 cells. Cells lacking Ligase4, an NHEJ Enzyme, are hypersensitive to GES. Furthermore, the sensitivity of Ligase4-/- cells was associated with enhanced DNA damage when comparing the accumulation of γ-H2AX foci and number of chromosomal aberrations (CAs) with WT cells. In addition, cells lacking Rad54, a HR Enzyme, also presented hypersensitivity and increased DNA damages in response to GES. Meanwhile, Treatment of GES-lacking enhanced the accumulation of RAD51, an HR factor, in TK6 cells, especially in Ligase4-/- . These results provided direct evidence that GES induced DSBs in TK6 cells and clarified that both NHEJ and HR were involved in the repair of GES-induced DNA damage, suggesting that GES in combination with inhibition of NHEJ or HR would provide a potential Anticancer strategy.

Keywords

DNA damage; genistein (GES); homologous recombination (HR); non-homologous DNA end joining (NHEJ).

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