Prindull Gregor
Department of Pediatrics, University of Göttingen, Göttingen, Germany.
Exp Hematol. 2008 Nov;36(11):1403-16. doi: 10.1016/j.exphem.2008.07.009.
Processing of epigenomic transcriptional information by cell cycle phase G(1) and decision-making at checkpoint G(1)/S are the final organizational steps preceding gene replication in transcriptional reorientation programs (i.e., switches from proliferation to cycle arrest and neoplastic transformation). Further analyses of cycle progression will open up new approaches in antineoplastic therapy.
The following bibliographic databases were consulted: Central Medical Library Cologne, PubMed (English), the last search was done on April 23,2008 and key words searched were: cell cycle, cell memory, DNA methylation, embryonal/neoplastic stem cells, enzyme-modulated chromatin, G(1)-G(1)/S checkpoint, genomic/epigenomics, genomic viral DNA, histones, telomere/telomerases, transcription factors, neoplastic transformation, senescence.
Gene transcription and epigenomic surveillance form a functional entity. In proliferation programs, transcriptional information is mediated by chromatin and DNA methylation, analyzed and processed in G(1) phase, and converged on the parental checkpoint G(1)/S for final decision-making on DNA replication. Genomic reorientation appears to be associated with transcriptional instability, which normally is corrected, possibly during the G(2)/M phase, to new levels of epigenomic equilibria. We speculate that daughter stem cells inherit persistent neoplasm-specific transcriptional instabilities through failure of the parental G(1)/S checkpoint. Foreign, silenced, potentially oncogenic DNA sequences, i.e. regular components of the human genome such as endogenous retroviruses, could conceivably be activated for expression in neoplastic transformation by epigenomic histone deacetylase/acetyl transferase/histone methyltransferase-mixed lineage leukemia deregulations.
Failure of cell cycle G(1)/S decision-making for DNA replication is the final and possibly a major cause in neoplastic transformation. Therefore, further analysis of the dynamics of G(1)-G(1)/Sphases could provide new opportunities for therapeutic strategies.
在转录重定向程序（即从增殖转变为细胞周期停滞和肿瘤转化）中，细胞周期G1期对表观基因组转录信息的处理以及在G1/S检查点的决策是基因复制之前的最后组织步骤。对细胞周期进程的进一步分析将为抗肿瘤治疗开辟新途径。
查阅了以下文献数据库：科隆中央医学图书馆、PubMed（英文），最后一次检索于2008年4月23日进行，检索关键词为：细胞周期、细胞记忆、DNA甲基化、胚胎/肿瘤干细胞、酶调节染色质、G1-G1/S检查点、基因组/表观基因组学、基因组病毒DNA、组蛋白、端粒/端粒酶、转录因子、肿瘤转化、衰老。
基因转录和表观基因组监测形成一个功能实体。在增殖程序中，转录信息由染色质和DNA甲基化介导，在G1期进行分析和处理，并在亲代G1/S检查点汇聚，以对DNA复制做出最终决策。基因组重定向似乎与转录不稳定性有关，这种不稳定性通常在G2/M期可能被校正到新的表观基因组平衡水平。我们推测子代干细胞通过亲代G1/S检查点功能障碍继承了持续的肿瘤特异性转录不稳定性。外来的、沉默的、潜在致癌的DNA序列，即人类基因组的常规组成部分，如内源性逆转录病毒，可能通过表观基因组组蛋白脱乙酰酶/乙酰转移酶/组蛋白甲基转移酶-混合谱系白血病失调而被激活，从而在肿瘤转化中表达。
细胞周期G1/S检查点对DNA复制的决策失败是肿瘤转化的最终且可能是主要原因。因此，对G1-G1/S期动力学的进一步分析可为治疗策略提供新机会。
