Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 subunit of DNA polymerase δ revealed in individual cells by cytometry.
Initiation and termination of DNA replication during S phase in relation to cyclins D1, E and A, p21WAF1, Cdt1 and the p12 subunit of DNA polymerase δ revealed in individual cells by cytometry.
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DOI：
10.18632/oncotarget.4149
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发表时间：
2015-05-20
期刊：
影响因子：
--
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Darzynkiewicz Z;Zhao H;Zhang S;Lee MY;Lee EY;Zhang Z
在我们最近对人类DNA聚合酶δ在准备DNA复制或修复过程中的调控机制的研究中，以激光扫描细胞仪为代表的多参数成像细胞术被用来评估与DNA复制启动相关的下列核蛋白的表达变化：细胞周期蛋白A、增殖细胞核抗原、Ki-67、p21WAF1、DNA复制因子CDT1和DNA聚合酶δ的最小亚基p12。在目前的综述中，我们不是集中于POLδ，而是强调LSC在这些研究中的应用，并概述了结合核蛋白表达对DNA复制进行并发差异分析所提供的可能性。目前提供了关于EDU掺入速率、可能报告的DNA复制和这些蛋白质的表达之间的相关性的更广泛的数据分析。新的数据，特别是与EDU掺入有关的Cyclin D1和Cyclin E的表达，以及Cyclin A与p21WAF1和Ki-67与CDT1的表达之间的关系，也被报道。特别令人感兴趣的是观察到，这种方法使评估细胞周期蛋白d1、p21WAF1、cdt1和p12的降解的时间序列成为可能，每一个都与DNA复制的启动和彼此相关。此外，还评估了这些蛋白质在DNA复制终止后在G2中的序列或再现。回顾的数据提供了潜在标记的更全面的呈现，其存在或不存在标志着DNA复制细胞。还讨论了这些标记物作为癌症组织中增殖活性的指标的有用性，这些指标可能承载着肿瘤进展的信息，并具有预后价值。
During our recent studies on mechanism of the regulation of human DNA polymerase δ in preparation for DNA replication or repair, multiparameter imaging cytometry as exemplified by laser scanning cytometry (LSC) has been used to assess changes in expression of the following nuclear proteins associated with initiation of DNA replication: cyclin A, PCNA, Ki-67, p21WAF1, DNA replication factor Cdt1 and the smallest subunit of DNA polymerase δ, p12. In the present review, rather than focusing on Pol δ, we emphasize the application of LSC in these studies and outline possibilities offered by the concurrent differential analysis of DNA replication in conjunction with expression of the nuclear proteins. A more extensive analysis of the data on a correlation between rates of EdU incorporation, likely reporting DNA replication, and expression of these proteins, is presently provided. New data, specifically on the expression of cyclin D1 and cyclin E with respect to EdU incorporation as well as on a relationship between expression of cyclin A vs. p21WAF1 and Ki-67 vs. Cdt1, are also reported. Of particular interest is the observation that this approach makes it possible to assess the temporal sequence of degradation of cyclin D1, p21WAF1, Cdt1 and p12, each with respect to initiation of DNA replication and with respect to each other. Also the sequence or reappearance of these proteins in G2 after termination of DNA replication is assessed. The reviewed data provide a more comprehensive presentation of potential markers, whose presence or absence marks the DNA replicating cells. Discussed is also usefulness of these markers as indicators of proliferative activity in cancer tissues that may bear information on tumor progression and have a prognostic value.
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影响因子：
3.7
作者：
Berniak, K.;Rybak, P.;Bernas, T.;Zarebski, M.;Biela, E.;Zhao, H.;Darzynkiewicz, Z.;Dobrucki, J. W.
通讯作者：
Dobrucki, J. W.
影响因子：
5.6
作者：
COHEN, LS;STUDZINSKI, GP
通讯作者：
STUDZINSKI, GP
影响因子：
5.6
作者：
DARZYNKIEWICZ, Z;EVENSON, DP;MELAMED, ML
通讯作者：
MELAMED, ML
影响因子：
64.8
作者：
Chang, Leifu;Zhang, Ziguo;Yang, Jing;McLaughlin, Stephen H.;Barford, David
通讯作者：
Barford, David
影响因子：
8.5
作者：
BRUNO, S;DARZYNKIEWICZ, Z
通讯作者：
DARZYNKIEWICZ, Z