Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding.
Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding.
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DOI：
10.1038/nchembio.422
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发表时间：
2010-10
影响因子：
14.8
通讯作者：
Shen, Binghui
中科院分区：
文献类型：
--
作者：
Guo, Zhigang;Zheng, Li;Xu, Hong;Dai, Huifang;Zhou, Mian;Pascua, Mary Rose;Chen, Qin M.;Shen, Binghui
FEN1是一种结构特异性的内切和外切核酸酶，具有多种决定细胞增殖和死亡等重要生物学过程的功能。因此，这种酶必须受到精确的调控，才能在正确的时间和特定的亚细胞位置执行其每一项功能。在这里，我们报告了FEN1在精氨酸残基上甲基化，主要是在R192。在S187，甲基化抑制FEN1的磷酸化。甲基化形式的FEN1，而不是磷酸化形式的FEN1，与增殖细胞核抗原(PCNA)强烈相互作用，确保其反应的开启和关闭时间。FEN1突变破坏精氨酸甲基化和增殖细胞核抗原的相互作用，导致非程序性磷酸化，并导致其在DNA复制或修复中心的定位失败。这导致冈崎基因片段成熟缺陷，细胞周期进程延迟，DNA修复受损，全基因组突变频率高。
Flap endonuclease 1 (FEN1), a structure-specific endo- and exo- nuclease, exhibits multiple functions that determine essential biological processes, such as cell proliferation and cell death. As such, the enzyme must be precisely regulated in order to execute each of its functions with the right timing and in a specific subcellular location. Here, we report that FEN1 is methylated at arginine residues, primarily at R192. The methylation suppresses FEN1 phosphorylation at S187. The methylated form, but not the phosphorylated form of FEN1, strongly interacts with Proliferating Cell Nuclear Antigen (PCNA), ensuring the on and off timing of its reaction. Mutations of FEN1 disrupting arginine methylation and PCNA interaction result in unscheduled phosphorylation and cause failure of its localization to DNA replication or repair foci. This consequently leads to a defect in Okazaki fragment maturation, a delay of cell cycle progression, impairment of DNA repair, and high frequency of genome-wide mutations.
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影响因子：
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