Abstract
Wuho known as WDR4 encodes a highly conserved WD40-repeat protein, which has known homologues of WDR4 in human and mouse. Wuho-FEN1 interaction may have a critical role in the growth and development, and in the maintenance of genome stability. However, how Wuho gene deletion contributes to cell growth inhibition and apoptosis is still unknown. We utilized CAGGCre-ER transgenic mice have a tamoxifen-inducible cre-mediated recombination cassette to prepare primary mouse embryonic fibroblasts (MEFs) with Wuho deficiency. We have demonstrated that Wuho deficiency would induces γH2AX protein level elevation, heterochromatin relaxation and DNA damage down-stream sequences, including p53 activation, caspase-mediated apoptotic pathway, and p21-mediated G2/M cell cycle arrest.
Keywords:
Apoptosis; Cell cycle arrest; DNA damage; Wuho; p53.
Copyright © 2018 Elsevier Inc. All rights reserved.
MeSH terms
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Animals
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Apoptosis* / drug effects
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Cell Line
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Cell Proliferation* / drug effects
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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DNA Damage* / drug effects
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Fibroblasts / cytology
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Fibroblasts / metabolism
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G2 Phase Cell Cycle Checkpoints / drug effects
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GTP-Binding Proteins / antagonists & inhibitors
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GTP-Binding Proteins / deficiency
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GTP-Binding Proteins / genetics*
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GTP-Binding Proteins / metabolism
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Histones / metabolism
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Mice
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Mice, Knockout
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RNA Interference
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RNA, Small Interfering / metabolism
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Tamoxifen / pharmacology
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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Cyclin-Dependent Kinase Inhibitor p21
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H2AX protein, mouse
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Histones
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RNA, Small Interfering
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Tumor Suppressor Protein p53
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Tamoxifen
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GTP-Binding Proteins
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WDR4 protein, mouse