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.

被称为WDR4的Wuho编码高度保守的WD40重复蛋白，该蛋白在人和小鼠中具有WDR4的同源物。Wuho-FEN1相互作用可能在生长发育和维持基因组稳定性中起关键作用。然而，Wuho基因缺失如何导致细胞生长抑制和凋亡仍然未知。我们利用具有他莫昔芬诱导的cre介导的重组盒的CAGGCre-ER转基因小鼠来制备具有Wuho缺陷的原代小鼠胚胎成纤维细胞（MEF）。我们已经证明，Wuho缺乏会诱导γH2AX蛋白水平升高，异染色质松弛和DNA损伤下游序列，包括p53激活，胱天蛋白酶介导的凋亡途径和p21介导的G2 / M细胞周期阻滞。