2. Academic Validation
  3. Filia Is an ESC-Specific Regulator of DNA Damage Response and Safeguards Genomic Stability

Filia Is an ESC-Specific Regulator of DNA Damage Response and Safeguards Genomic Stability

  • Cell Stem Cell. 2015 Jun 4;16(6):684-98. doi: 10.1016/j.stem.2015.03.017.
Bo Zhao 1,  Wei-Dao Zhang 2,  Ying-Liang Duan 1,  Yong-Qing Lu 1,  Yi-Xian Cun 1,  Chao-Hui Li 2,  Kun Guo 2,  Wen-Hui Nie 3,  Lei Li 4,  Rugang Zhang 5,  Ping Zheng 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Yunnan Key Laboratory of Animal Reproduction, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
  • 2 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Yunnan Key Laboratory of Animal Reproduction, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China.
  • 3 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
  • 4 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 5 Gene Expression and Regulation Program, The Wistar Institute Cancer Center, The Wistar Institute, Philadelphia, PA 19104, USA.
  • 6 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Yunnan Key Laboratory of Animal Reproduction, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China. Electronic address: zhengp@mail.kiz.ac.cn.
PMID: 25936915 DOI: 10.1016/j.stem.2015.03.017
Abstract

Pluripotent stem cells (PSCs) hold great promise in cell-based therapy, but the genomic instability seen in culture hampers their full application. A greater understanding of the factors that regulate genomic stability in PSCs could help address this issue. Here we describe the identification of Filia as a specific regulator of genomic stability in mouse embryonic stem cells (ESCs). Filia expression is induced by genotoxic stress. Filia promotes centrosome integrity and regulates the DNA damage response (DDR) through multiple pathways, including DDR signaling, cell-cycle checkpoints and damage repair, ESC differentiation, and Apoptosis. Filia depletion causes ESC genomic instability, induces resistance to Apoptosis, and promotes malignant transformation. As part of its role in DDR, Filia interacts with PARP1 and stimulates its enzymatic activity. Filia also constitutively resides on centrosomes and translocates to DNA damage sites and mitochondria, consistent with its multifaceted roles in regulating centrosome integrity, damage repair, and Apoptosis.

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