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Effect of polyamine deficiency on proteins involved in Okazaki fragment maturation.

机译:多胺缺乏对冈崎片段成熟中涉及的蛋白质的影响。

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Polyamine depletion causes S phase prolongation, and earlier studies indicate that the elongation step of DNA replication is affected. This led us to investigate the effects of polyamine depletion on enzymes crucial for Okazaki fragment maturation in the two breast cancer cell lines MCF-7 and L56Br-C1. In MCF-7 cells, treatment with N(1),N(11)-diethylnorspermine (DENSPM) causes S phase prolongation. In L56Br-C1 cells the prolongation is followed by massive apoptosis. In the present study we show that L56Br-C1 cells have substantially lower basal expressions of two Okazaki fragment maturation key proteins, DNA ligase I and FEN1, than MCF-7 cells. Thus, these two proteins might be promising markers for prediction of polyamine depletion sensitivity, something that can be useful for cancer treatment with polyamine analogues. DENSPM treatment affects the cellular distribution of FEN1 in L56Br-C1 cells, but not in MCF-7 cells, implying that FEN1 is affected by or involved in DENSPM-induced apoptosis.
机译:多胺耗竭导致S期延长,早期的研究表明DNA复制的延长步骤受到影响。这导致我们研究了多胺消耗对两种乳腺癌细胞MCF-7和L56Br-C1中冈崎片段成熟至关重要的酶的影响。在MCF-7细胞中,用N(1),N(11)-二乙基去甲精胺(DENSPM)处理会导致S期延长。在L56Br-C1细胞中,延长之后是大量细胞凋亡。在本研究中,我们显示L56Br-C1细胞的两个Okazaki片段成熟关键蛋白(DNA连接酶I和FEN1)的基础表达比MCF-7细胞低得多。因此,这两种蛋白质可能是预测多胺消耗敏感性的有前途的标志物,可用于多胺类似物的癌症治疗。 DENSPM处理会影响FEN1在L56Br-C1细胞中的细胞分布,但不会影响MCF-7细胞,这暗示FEN1受DENSPM诱导的凋亡影响或与之相关。

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