缺乏FEN-1核酸内切酶的脊椎动物细胞是有活力的，但对甲基化试剂和过氧化氢高度敏感。
Vertebrate cells lacking FEN-1 endonuclease are viable but hypersensitive to methylating agents and H2O2.
作者信息
Matsuzaki Yasuo, Adachi Noritaka, Koyama Hideki
机构信息
Kihara Institute for Biological Research and Graduate School of Integrated Science, Yokohama City University, Maioka-cho 641-12, Totsuka-ku, Yokohama 244-0813, Japan.
出版信息
Nucleic Acids Res. 2002 Jul 15;30(14):3273-7. doi: 10.1093/nar/gkf440.
Abstract
The structure-specific FEN-1 endonuclease has been implicated in various cellular processes, including DNA replication, repair and recombination. In vertebrate cells, however, no in vivo evidence has been provided so far. Here, we knocked out the FEN-1 gene (FEN1) in the chicken DT40 cell line. Surprisingly, homozygous mutant (FEN1-/-) cells were viable, indicating that FEN-1 is not essential for cell proliferation and thus for Okazaki fragment processing during DNA replication. However, compared with wild-type cells, FEN1-/- cells exhibited a slow growth phenotype, probably due to a high rate of cell death. The mutant cells were hypersensitive to methylmethane sulfonate, N-methyl-N'-nitro-N-nitrosoguanidine and H2O2, but not to UV light, X-rays and etoposide, suggesting that FEN-1 functions in base excision repair in vertebrate cells.
摘要
结构特异性的FEN-1核酸内切酶参与了多种细胞过程，包括DNA复制、修复和重组。然而，在脊椎动物细胞中，目前尚未有体内证据。在此，我们在鸡DT40细胞系中敲除了FEN-1基因（FEN1）。令人惊讶的是，纯合突变体（FEN1-/-）细胞是存活的，这表明FEN-1对于细胞增殖以及DNA复制过程中的冈崎片段加工并非必不可少。然而，与野生型细胞相比，FEN1-/-细胞表现出生长缓慢的表型，这可能是由于细胞死亡率较高所致。突变细胞对甲基磺酸甲酯、N-甲基-N'-硝基-N-亚硝基胍和H2O2高度敏感，但对紫外线、X射线和依托泊苷不敏感，这表明FEN-1在脊椎动物细胞的碱基切除修复中发挥作用。
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