A distinct first replication cycle of DNA introduced in mammalian cells
A distinct first replication cycle of DNA introduced in mammalian cells
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DOI：
10.1093/nar/gkq903
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发表时间：
2011-03-01
影响因子：
14.9
通讯作者：
Krasilnikova, Maria M.
中科院分区：
文献类型：
--
作者：
Chandok, Gurangad S.;Kapoor, Kalvin K.;Krasilnikova, Maria M.
微卫星DNA序列中的许多突变事件可以追溯到第一次胚胎分裂。目前还不知道是什么使胚胎DNA的第一个复制周期与随后的复制周期不同。在这里，我们证明了一个不寻常的复制模式是参与在哺乳动物细胞中引入的DNA复制的第一个周期。这种替代复制从随机位置开始，并在染色质完全组装之前发生。在各种细胞系和原代细胞中检测到。单链区域的存在增加了这种替代复制模式的效率。选择性复制不能通过富含A/T的FRA 16 B脆性位点进行，而常规复制模式不受其影响。富含A/T的微卫星与癌症中大多数染色体断点相关。我们认为，在胚胎和癌细胞中，这种替代性复制模式可能起始于具有不成熟染色质结构的区域，从而导致基因组不稳定性增加。这项工作表明，第一次，在哺乳动物细胞中的第一个和随后的复制周期的复制进展的差异。
Many mutation events in microsatellite DNA sequences were traced to the first embryonic divisions. It was not known what makes the first replication cycles of embryonic DNA different from subsequent replication cycles. Here we demonstrate that an unusual replication mode is involved in the first cycle of replication of DNA introduced in mammalian cells. This alternative replication starts at random positions, and occurs before the chromatin is fully assembled. It is detected in various cell lines and primary cells. The presence of single-stranded regions increases the efficiency of this alternative replication mode. The alternative replication cannot progress through the A/T-rich FRA16B fragile site, while the regular replication mode is not affected by it. A/T-rich microsatellites are associated with the majority of chromosomal breakpoints in cancer. We suggest that the alternative replication mode may be initiated at the regions with immature chromatin structure in embryonic and cancer cells resulting in increased genomic instability. This work demonstrates, for the first time, differences in the replication progression during the first and subsequent replication cycles in mammalian cells.