Multiple roles of vertebrate REV genes in DNA repair and recombination
Multiple roles of vertebrate REV genes in DNA repair and recombination
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DOI：
10.1128/mcb.25.14.6103-6111.2005
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Takeda, S
中科院分区：
文献类型：
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作者：
Okada, T;Sonoda, E;Takeda, S
在酵母中，Rev1、Rev3和Rev7参与了各种DNA损伤、自发和紫外线诱导的突变的跨损伤合成。在这里，我们干扰了鸡B淋巴细胞系DT40中的Rev1、Rev3和Rev7。Rev1(-/-)Rev3(-/-)Rev7(-/-)细胞表现出自发细胞死亡、染色体不稳定/脆性以及对各种基因毒性处理的超敏反应。令人惊讶的是，三重敲除细胞的姐妹染色单体交换(SCE)水平受到抑制，这可能反映了同源重组介导的复制后修复事件，而每个单个突变体的姐妹染色单体交换水平都升高。此外，Rev1(-/-)细胞以及三个突变体显示免疫球蛋白基因转换水平降低，这表明Rev1参与了基于重组的途径。本研究使我们对三个REV分子的协同功能以及Rev1在脊椎动物细胞中的非依赖于Pol Zeta(Rev3-Rev7)的作用有了新的认识。
in yeast, Rev1, Rev3, and Rev7 are involved in translesion synthesis over various kinds of DNA damage and spontaneous and UV-induced mutagenesis. Here, we disrupted Rev1, Rev3, and Rev7 in the chicken B-lymphocyte line DT40. REV1(-/-) REV3(-/-) REV7(-/-) cells showed spontaneous cell death, chromosomal instability/fragility, and hypersensitivity to various genotoxic treatments as observed in each of the single mutants. Surprisingly, the triple-knockout cells showed a suppressed level of sister chromatid exchanges (SCEs), which may reflect postreplication repair events mediated by homologous recombination, while each single mutant showed an elevated SCE level. Furthermore, REV1(-/-) cells as well as triple mutants showed a decreased level of immunoglobulin gene conversion, suggesting participation of Rev1 in a recombination-based pathway. The present study gives us a new insight into cooperative function of three Rev molecules and the Pol zeta (Rev3-Rev7) -independent role of Rev1 in vertebrate cells.