Single-molecule analysis reveals that DNA replication dynamics vary across the course of schizogony in the malaria parasite Plasmodium falciparum.
Single-molecule analysis reveals that DNA replication dynamics vary across the course of schizogony in the malaria parasite Plasmodium falciparum.
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DOI：
10.1038/s41598-017-04407-z
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发表时间：
2017-06-21
影响因子：
4.6
通讯作者：
Merrick CJ
中科院分区：
文献类型：
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作者：
Stanojcic S;Kuk N;Ullah I;Sterkers Y;Merrick CJ
DNA复制和细胞周期的机制在模式生物中得到了很好的表征，但对早期发散顶复门寄生虫细胞生物学的这些基本方面知之甚少，这些寄生虫不通过典型的二分裂，而是经历非常规的周期。疟原虫的裂殖生殖在胞质分裂之前通过独立的异步轮的基因组复制产生~16 - 24个新的细胞核，并且关于促进这一点的DNA复制的控制知之甚少。我们已经表征了恶性疟原虫在整个胚胎发育过程中的复制动力学，使用DNA纤维标记和梳理在单分子水平上可视化复制叉。我们发现，起源是非常紧密的疟原虫相比，大多数模型系统，复制动力学在整个过程中的寄生虫，从更快的合成速率和更广泛的间隔起源通过较慢的合成速率和更紧密的间隔起源。这与人类细胞中通常在S期看到的模式相反，当单个基因组复制时。复制分支在整个系统中也以异常高的速度停滞。我们的工作以前所未有的细节探索了疟原虫DNA复制，并为分析细胞周期动力学和开发针对疟疾生物学这一独特方面的干预措施开辟了巨大的空间。
The mechanics of DNA replication and cell cycling are well-characterized in model organisms, but less is known about these basic aspects of cell biology in early-diverging Apicomplexan parasites, which do not divide by canonical binary fission but undergo unconventional cycles. Schizogony in the malaria parasite, Plasmodium, generates ~16–24 new nuclei via independent, asynchronous rounds of genome replication prior to cytokinesis and little is known about the control of DNA replication that facilitates this. We have characterised replication dynamics in P. falciparum throughout schizogony, using DNA fibre labelling and combing to visualise replication forks at a single-molecule level. We show that origins are very closely spaced in Plasmodium compared to most model systems, and that replication dynamics vary across the course of schizogony, from faster synthesis rates and more widely-spaced origins through to slower synthesis rates and closer-spaced origins. This is the opposite of the pattern usually seen across S-phase in human cells, when a single genome is replicated. Replication forks also appear to stall at an unusually high rate throughout schizogony. Our work explores Plasmodium DNA replication in unprecedented detail and opens up tremendous scope for analysing cell cycle dynamics and developing interventions targetting this unique aspect of malaria biology.