Domaines Chromatiniens et Réplication, Institut Jacques Monod, UMR7592 CNRS - Université Paris Diderot, Paris, France, Equipe labellisée ARC.
Laboratoire d'Informatique Gaspard-Monge, UMR8049, ESIEE, Noisy Le Grand, France.
Nucleic Acids Res. 2019 Jun 4;47(10):5155-5169. doi: 10.1093/nar/gkz220.
Eukaryotic genomes are replicated under the control of a highly sophisticated program during the restricted time period corresponding to S phase. The most widely used replication timing assays, which are performed on populations of millions of cells, suggest that most of the genome is synchronously replicated on homologous chromosomes. We investigated the stochastic nature of this temporal program, by comparing the precise replication times of allelic loci within single vertebrate cells progressing through S phase at six loci replicated from very early to very late. We show that replication timing is strictly controlled for the three loci replicated in the first half of S phase. Out of the three loci replicated in the second part of S phase, two present a significantly more stochastic pattern. Surprisingly, we find that the locus replicated at the very end of S phase, presents stochasticity similar to those replicated in early S phase. We suggest that the richness of loci in efficient origins of replication, which decreases from early- to late-replicating regions, and the strength of interaction with the nuclear lamina may underlie the variation of timing control during S phase.
真核生物基因组在 S 期这个特定时间段内，通过一个高度复杂的程序来进行复制。目前应用最广泛的复制时间测定方法是对几百万个细胞群体进行检测，该方法表明大部分基因组的同源染色体是同步复制的。为了研究该时间程序的随机性，我们对处于 S 期的单个脊椎动物细胞中的等位基因座在六个从极早期到极晚期复制的位点上的精确复制时间进行了比较。我们发现，在 S 期前半部分复制的三个基因座的复制时间受到严格控制。而在 S 期后半部分复制的三个基因座中，有两个呈现出明显更随机的模式。令人惊讶的是，我们发现 S 期末期复制的基因座与 S 期早期复制的基因座具有相似的随机性。我们认为，从早期复制区域到晚期复制区域，高效复制起点的基因座数量减少，以及与核纤层的相互作用强度，可能是 S 期时间控制变化的基础。
