DNA replication timing is deterministic at the level of chromosomal domains but stochastic at the level of replicons in Xenopus egg extracts
DNA replication timing is deterministic at the level of chromosomal domains but stochastic at the level of replicons in Xenopus egg extracts
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DOI：
10.1093/nar/gkn533
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发表时间：
2008-10-01
影响因子：
14.9
通讯作者：
Marheineke, Kathrin
中科院分区：
文献类型：
--
作者：
Labit, Helene;Perewoska, Irene;Marheineke, Kathrin
非洲爪蟾卵提取物中的复制起点位于明显的随机序列，但在ATR/ATM激酶的控制下，在S期的不同时间被激活成簇。我们调查了是否染色体域和单序列复制在不同的时间在S期的鸡蛋提取物。复制灶逐渐出现在早期的S期和病灶标记早期在一个S期共定位与那些标记早期在下一个S期。然而，这两个早期标签的分布并不符合单一起源或起源集群之间的单一DNA纤维。4 Mb非洲爪蟾rDNA重复域被发现复制晚于其余的基因组，并具有更耐核酸酶的染色质结构。转录单位比基因间间隔区更频繁地启动复制。这些结果首次表明，在这种胚胎系统中，转录不发生，复制时间是确定性的大染色质结构域（1-5 Mb）的规模，但随机复制子（10 kb）和复制子簇（50-100 kb）的规模。
Replication origins in Xenopus egg extracts are located at apparently random sequences but are activated in clusters that fire at different times during S phase under the control of ATR/ATM kinases. We investigated whether chromosomal domains and single sequences replicate at distinct times during S phase in egg extracts. Replication foci were found to progressively appear during early S phase and foci labelled early in one S phase colocalized with those labelled early in the next S phase. However, the distribution of these two early labels did not coincide between single origins or origin clusters on single DNA fibres. The 4Mb Xenopus rDNA repeat domain was found to replicate later than the rest of the genome and to have a more nuclease-resistant chromatin structure. Replication initiated more frequently in the transcription unit than in the intergenic spacer. These results suggest for the first time that in this embryonic system, where transcription does not occur, replication timing is deterministic at the scale of large chromatin domains (1-5 Mb) but stochastic at the scale of replicons (10 kb) and replicon clusters (50-100 kb).