白色念珠菌是一种多形态的人类致病真菌，存在三种形态：酵母形态，假菌丝形态与真菌丝形态。白色念珠菌三种形态之间的转化对其致病性与感染能力非常关键。cAMP/PKA途径和MAPK途径是白色念珠菌控制菌丝生长的两条途径，而最近研究表明触发DNA检验点反应也能导致丝状生长。蛋白磷酸酶4（PP4）是丝/苏氨酸蛋白磷酸酶PP2A家族的重要成员，是一种在进化中高度保守的蛋白磷酸酶。PP4c通过与不同的调节亚基形成磷酸酶复合体，在体内参与调节多项生物学功能，例如：中心体成熟，DNA损伤修复等。其中，在酿酒酵母、线虫、果蝇、哺乳动物中,PP4同源物均在DNA损伤修复中发挥重要作用。本文中，通过基因敲除技术，我们在白色念珠菌中对PP4复合体亚基的同源物CaPph3与CaPsy2功能进行研究。结果发现Capph3Δ和Capsy2Δ不影响细胞的形态和生长，以及血清诱导真菌丝的过程，但是能抑制Spider与SLAD培养基诱导的菌丝发生。Capph3Δ和Capsy2Δ对MMS，顺铂以及紫外线（UV）等遗传毒性造成DNA损伤的条件具有很高的敏感性，并且出现假菌丝生长，细胞周期S期阻滞现象；当去除MMS与顺铂的作用，细胞从DNA损伤状态恢复的过程中，Capph3Δ和Capsy2Δ不能恢复正常细胞形态和细胞周期，而是呈现持续性的丝状生长与持续性的细胞周期阻滞，并且侵入性增加。因此，CaPph3与CaPsy2可能在白色念珠菌DNA损伤检验点反应、细胞从DNA损伤中恢复，以及形态发生中发挥重要作用。

The human polymorphic fungal pathogen, Candida albicans, can grow in at least three different morphologies: yeast, pseudohypae and hyphae. The ablility to switch between the yeast form and hyphae form seems to play critical roles in its infection and virulence. In C. albicans the cAMP/PKA pathway and MAPK pathway are two mainly pathways which regulate hyphae and pseudohyphae growth respectively. Recent work shows that C. albicans can switch to filamentous growth under genotoxic stress in a manner dependent on the DNA replication/damage checkpoint.Protein phosphatase 4(PP4) is a PP2A-type serine/threonine phosphatase, which is a highly conserved phosphatase in many species. By interacting with different regulatory subunit, PP4c forms several phosphatase complexes and regulates some cellular processes, such as microtubule growth, centrosome maturation and DNA damage checkpoint. Interestingly, critical roles of PP4 complex in DNA damage response were found in budding yeast, C. elegans, D. melanogaster and mammlian.Here, by using gene knockout technique, we have investigated the function of CaPph3 and CaPsy2 in C. albicans whose orthlogue in mammalian is PP4. Deleting CaPPH3 and CaPSY2 don’t affect morphogenesis and growth rate in normal culture condition. Capph3Δ and Capsy2Δ can still switch to hyphae growth in the presence of serum, but inhibit hyphae growth induced by Spider or SLAD media. Capph3Δ and Capsy2Δexhibit hypersensitivity to DNA damaging agents such as MMS, cisplatin,and UV, and switch to pseudohyphae growth. Cell cycle was arrested in intra-S phase in Capph3Δ and Capsy2Δ under these genotoxic stress. Further more, after removing MMS or cisplatin and shifting the cell to fresh media without drug, Capph3Δ and Capsy2Δ fail to revert to yeast growth and exhibit continuous filamentous growth, whereas wild-type SC5314 can resume to normal yeast growth and normal cell cycle,. FACS shows the cell cycle of Capph3Δ and Capsy2Δ is still arrested during the recovery from DNA damage. Therefore, our data reveals that CaPph3 and CaPsy2 may have critical roles in DNA damage response, recovery from DNA damage, and cell morphogenesis in C. albicans.