Mateos Santiago, Domínguez Inmaculada, Cantero Gloria, Pastor Nuria, Campanella Claudia, Cortés Felipe
Department of Cell Biology, Faculty of Biology, University of Seville, Avda Reina Mercedes 6, 41012 Seville, Spain.
Mutat Res. 2008 Sep 26;644(1-2):24-30. doi: 10.1016/j.mrfmmm.2008.06.007. Epub 2008 Jul 1.
It has been recently proposed that hypomethylation of DNA induced by 5-azacytidine (5-azaC) leads to reduced chromatid decatenation that ends up in endoreduplication, most likely due to a failure in topo II function [S. Mateos, I. Domínguez, N. Pastor, G. Cantero, F. Cortés, The DNA demethylating 5-azaC induces endoreduplication in cultured Chinese hamster cells, Mutat. Res. 578 (2005) 33-42]. The Chinese hamster mutant cell line EM9 has a high spontaneous frequency of endoreduplication as compared to its parental line AA8. In order to see if this is related to the degree of DNA methylation, we have investigated the basal levels of both endpoints in AA8 and EM9, as well as the effect of extensive 5-azaC-induced demethylation on the production of endoreduplication. Based on the correlation between the levels of DNA methylation and indices of endoreduplication we propose that genomic DNA hypomethylation in EM9 cell line is probably an important factor that bears significance in relation to the high basal level of endoreduplication observed in this cell line.
最近有人提出，5-氮杂胞苷（5-azaC）诱导的DNA低甲基化会导致染色单体解连环作用减弱，最终导致核内复制，这很可能是由于拓扑异构酶II功能失效所致[S. 马特奥斯、I. 多明格斯、N. 帕斯托、G. 坎特罗、F. 科尔特斯，DNA去甲基化剂5-azaC诱导培养的中国仓鼠细胞发生核内复制，《突变研究》578（2005年）33 - 42页]。与亲本细胞系AA8相比，中国仓鼠突变细胞系EM9具有较高的自发核内复制频率。为了探究这是否与DNA甲基化程度有关，我们研究了AA8和EM9中这两个终点的基础水平，以及广泛的5-azaC诱导的去甲基化对核内复制产生的影响。基于DNA甲基化水平与核内复制指标之间的相关性，我们提出，EM9细胞系中的基因组DNA低甲基化可能是一个重要因素，与该细胞系中观察到的高基础核内复制水平有关。
