Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident
Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident
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DOI：
10.1016/s0960-9822(07)00563-5
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发表时间：
1998-12-03
期刊：
影响因子：
9.2
通讯作者：
Clevers, H
中科院分区：
文献类型：
--
作者：
Korver, W;Schilham, MW;Clevers, H
为了保持稳定的核型，真核细胞周期经过协调，使得每次有丝分裂之前只有一轮S期，在DNA复制完成之前不会启动有丝分裂。在控制这种协调的低等真核生物中，已经定义了几个检查点和调节蛋白，但对哺乳动物细胞中涉及的蛋白知之甚少。以前，我们已经证明了有翼螺旋转录因子三叉戟-也被称为HfH-11，FKL16和Win[1-3]-仅在周期细胞中表达，并在有丝分裂过程中被磷酸化[1，4]。三叉戟的细胞功能尚未被描述，然而，在这里，我们已经表明，三叉戟基因的破坏导致小鼠出生后死亡，很可能是由于循环衰竭。从胚胎第10天(E10)开始对三叉戟(-/-)胚胎的组织学分析显示，发育中的心肌有一种特殊的、特征性的缺陷，心肌细胞的取向高度不规则，这些紊乱的心肌细胞的细胞核明显是多倍体，DNA含量增加了50倍。在胚胎肝细胞中也观察到多倍体。我们的结果表明，三叉戟的表达是防止心脏和肝脏出现多轮S时相所必需的。因此，三叉戟似乎在防止DNA在G2和M期重新复制方面起到了作用。(C)现代生物有限公司ISSN 0960-9822。
In order to maintain a stable karyotype, the eukaryotic cell cycle is coordinated such that only one round of S phase precedes each mitosis, and mitosis is not initiated until DNA replication is completed. Several checkpoints and regulatory proteins have been defined in lower eukaryotes that govern this coordination, but little is known about the proteins that are involved in mammalian cells. Previously, we have shown that the winged-helix transcription factor Trident - also known as HFH-11, FKL16 and WIN [1-3] - is exclusively expressed in cycling cells and is phosphorylated during mitosis [1,4]. The cellular function of Trident has yet to be described, however, Here, we have shown that disruption of the Trident gene in mice resulted in postnatal death, most probably because of circulatory failure. Histological analysis of Trident(-/-) embryos from embryonic day 10 (E10) onwards revealed a specific, characteristic defect in the developing myocardium, The orientation of the myocytes was highly irregular and the nuclei of these disorganized cardiomyocytes were clearly polyploid with up to a 50-fold increase in DNA content. Polyploidy was also observed in embryonic hepatocytes. Our results indicate that expression of Trident is required to prevent multiple rounds of S phase in the heart and the liver. Trident therefore appears to have a role in preventing DNA re-replication during the G2 and M phases. (C) Current Biology Ltd ISSN 0960-9822.