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RAD51重组途径的失活会刺激哺乳动物细胞中紫外线诱导的诱变。

Inactivation of the RAD51 recombination pathway stimulates UV-induced mutagenesis in mammalian cells.

作者信息

Lambert Sarah, Lopez Bernard S

机构信息

UMR217 CNRS-CEA, CEA, Direction des Sciences du Vivant, Département de Radiobiologie et Radiopathologie, 60-68 avenue du Général Leclerc, 92 265 Fontenay aux Roses, cedex, France.

出版信息

Oncogene. 2002 Jun 6;21(25):4065-9. doi: 10.1038/sj.onc.1205535.

Abstract

We have examined the impact of the RAD51 recombination pathway on recombination and mutagenesis induced by UV-C in mammalian cells. We used hamster CHO cell lines that express different forms of Rad51 protein, resulting in stimulation or inhibition of spontaneous gene conversion. Spontaneous mutagenesis was affected by none of the RAD51 forms. The wild-type mouse MmRAD51 affects neither UV-induced recombination nor UV-induced mutagenesis. In contrast, the dominant negative SMRAD51 strongly impairs UV-induced recombination while it stimulates UV-induced mutagenesis. Our results show that a defect in the RAD51 gene conversion pathway reveals (a) mutagenic alternative pathway(s) to repair UV-damage, in mammalian cells.

摘要

我们研究了RAD51重组途径对哺乳动物细胞中紫外线C(UV-C)诱导的重组和诱变的影响。我们使用了表达不同形式Rad51蛋白的仓鼠CHO细胞系,从而导致自发基因转换受到刺激或抑制。自发诱变不受任何一种RAD51形式的影响。野生型小鼠MmRAD51既不影响紫外线诱导的重组,也不影响紫外线诱导的诱变。相比之下,显性负性SMRAD51强烈损害紫外线诱导的重组,同时刺激紫外线诱导的诱变。我们的结果表明,在哺乳动物细胞中,RAD51基因转换途径的缺陷揭示了一种(或多种)用于修复紫外线损伤的诱变替代途径。

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