PROCyTOX Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Fontenay-aux-Roses and Université Paris-Saclay, France.
Sci Rep. 2016 Sep 2;6:32510. doi: 10.1038/srep32510.
Telomeres are specific structures that protect chromosome ends and act as a biological clock, preventing normal cells from replicating indefinitely. Mammalian telomeres are replicated throughout S-phase in a predetermined order. However, the mechanism of this regulation is still unknown. We wished to investigate this phenomenon under physiological conditions in a changing environment, such as the immortalization process to better understand the mechanism for its control. We thus examined the timing of human telomere replication in normal and SV40 immortalized cells, which are cytogenetically very similar to cancer cells. We found that the timing of telomere replication was globally conserved under different conditions during the immortalization process. The timing of telomere replication was conserved despite changes in telomere length due to endogenous telomerase reactivation, in duplicated homologous chromosomes, and in rearranged chromosomes. Importantly, translocated telomeres, possessing their initial subtelomere, retained the replication timing of their homolog, independently of the proportion of the translocated arm, even when the remaining flanking DNA is restricted to its subtelomere, the closest chromosome-specific sequences (inferior to 500 kb). Our observations support the notion that subtelomere regions strongly influence the replication timing of the associated telomere.
端粒是一种特殊的结构，保护染色体末端，充当生物钟，防止正常细胞无限复制。哺乳动物的端粒在 S 期按预定顺序复制。然而，这种调节的机制仍然未知。我们希望在不断变化的环境（如永生化过程）的生理条件下研究这种现象，以便更好地理解其控制机制。因此，我们研究了正常和 SV40 永生化细胞中端粒复制的时间，这些细胞在细胞遗传学上与癌细胞非常相似。我们发现，在永生化过程中不同条件下，端粒复制的时间是全局保守的。尽管由于内源性端粒酶的重新激活、同源染色体的复制以及重排染色体导致端粒长度发生变化，但端粒复制的时间仍然保持不变。重要的是，即使剩余的侧翼 DNA仅限于其亚端粒（最接近的染色体特异性序列（小于 500kb）），具有初始亚端粒的易位端粒仍然保留其同源物的复制时间，而与易位臂的比例无关。我们的观察结果支持这样一种观点，即亚端粒区域强烈影响相关端粒的复制时间。
