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Genetic interaction between Ptc2 and protein phosphatase 4 (PP4) in the regulation of DNA damage response and virulence in Candida albicans.
FEMS Yeast Research ( IF 3.2 ) Pub Date : 2019-12-01 , DOI: 10.1093/femsyr/foz075
Jia Feng 1 , Aidi Shan 1 , Jing Hu 1 , Zhenyu Cao 1 , Rui Lv 1 , Jinrong Feng 1
Affiliation  

In the pathogenic fungus Candida albicans, phosphoregulation of the checkpoint kinase Rad53 plays a crucial role in the filamentous growth response to genotoxic stresses. The protein phosphatase 4 (PP4) complex, containing Pph3 and either Psy2 or Psy4, is proved to play a critical role in Rad53 dephosphorylation. In previous studies, we characterized CaPtc2 (the ortholog of both Ptc2 and Ptc3 in Saccharomyces cerevisiae) as a potential DNA-damage-related protein phosphatase. In this study, we checked the genetic interaction of PTC2 with the PP4 complex in the DNA damage response pathway. The results suggest that Ptc2 shows a negative genetic interaction with Pph3, but positive genetic interaction with either Psy2 or Psy4 in response to genotoxic stress. Deletion of PTC2 alone resulted in no significant change in cell virulence, but double deletion of PTC2 PPH3 significantly decreased virulence, while double deletions of either PTC2 PSY2 or PTC2 PSY4 caused virulence levels similar to that shown by PSY2 or PSY4 single-gene deletion cells. Taken together, we propose that Ptc2 in C. albicans plays a compensatory role for Pph3 but is dependent on Psy2 and Psy4 in regulation of DNA damage and cell virulence.

中文翻译:

Ptc2和蛋白磷酸酶4(PP4)之间的遗传相互作用调节白色念珠菌的DNA损伤反应和毒力。

在致病性真菌白色念珠菌中,检查点激酶Rad53的磷酸化在丝状生长对基因毒性胁迫的响应中起着至关重要的作用。包含Pph3和Psy2或Psy4的蛋白磷酸酶4(PP4)复合物被证明在Rad53脱磷酸中起关键作用。在以前的研究中,我们将CaPtc2(酿酒酵母中Ptc2和Ptc3的直系同源物)表征为潜在的DNA损伤相关蛋白磷酸酶。在这项研究中,我们检查了DNA损伤反应途径中PTC2与PP4复合物的遗传相互作用。结果表明,Ptc2与Pph3表现出负的遗传相互作用,而对Psy2或Psy4表现出遗传毒性的正响应。单独删除PTC2不会导致细胞毒力发生明显变化,但是PTC2 PPH3的两次缺失会显着降低毒力,而PTC2 PSY2或PTC2 PSY4的两次缺失会导致毒力水平与PSY2或PSY4单基因缺失细胞相似。两者合计,我们建议在白色念珠菌中Ptc2对Pph3起到补偿作用,但在调节DNA损伤和细胞毒性方面依赖于Psy2和Psy4。
更新日期:2019-11-01
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