Department Basic Medical Sciences, St. Georges University London, London, United Kingdom.
PLoS One. 2011;6(11):e27101. doi: 10.1371/journal.pone.0027101. Epub 2011 Nov 15.
A reduction in the level of some MCM proteins in human cancer cells (MCM5 in U20S cells or MCM3 in Hela cells) causes a rapid increase in the level of DNA damage under normal conditions of cell proliferation and a loss of viability when the cells are subjected to replication interference. Here we show that Drosophila S2 cells do not appear to show the same degree of sensitivity to MCM2-6 reduction. Under normal cell growth conditions a reduction of >95% in the levels of MCM3, 5, and 6 causes no significant short term alteration in the parameters of DNA replication or increase in DNA damage. MCM depleted cells challenged with HU do show a decrease in the density of replication forks compared to cells with normal levels of MCM proteins, but this produces no consistent change in the levels of DNA damage observed. In contrast a comparable reduction of MCM7 levels has marked effects on viability, replication parameters and DNA damage in the absence of HU treatment.
在人类癌细胞中,某些 MCM 蛋白(U20S 细胞中的 MCM5 或 Hela 细胞中的 MCM3)水平的降低会导致在正常细胞增殖条件下 DNA 损伤水平的迅速增加,并且在细胞受到复制干扰时会丧失活力。在这里,我们表明,果蝇 S2 细胞似乎对 MCM2-6 减少没有表现出相同程度的敏感性。在正常的细胞生长条件下,MCM3、5 和 6 的水平降低超过 95%,不会导致 DNA 复制参数的短期显著改变或 DNA 损伤的增加。与具有正常 MCM 蛋白水平的细胞相比,用 HU 处理耗尽 MCM 的细胞中复制叉的密度确实会降低,但这不会导致观察到的 DNA 损伤水平发生一致变化。相比之下,在没有 HU 处理的情况下,MCM7 水平的相当降低对细胞活力、复制参数和 DNA 损伤有明显影响。