The origin recognition complex is dispensable for endoreplication in Drosophila
The origin recognition complex is dispensable for endoreplication in Drosophila
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DOI：
10.1073/pnas.0805189105
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发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Asano, Maki
中科院分区：
文献类型：
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作者：
Park, So Young;Asano, Maki
起源识别复合体(ORC)是有丝分裂细胞周期复制前复合体(Pre-RC)的重要组成部分。ORC作为组装前RC的基础的作用从酵母到人类都是保守的。此外，在后生动物中，ORC在决定复制起始时间和起始点使用方面起着关键作用。在这份报告中，我们产生并分析了一个果蝇ORC1等位基因，以研究ORC1在发育过程中三种不同的DNA复制模式中的作用。正如预期的那样，ORC1对于大脑和成像盘的有丝分裂复制和增殖以及卵巢卵泡细胞的基因扩增都是必不可少的。然而，令人惊讶的是，ORC1不是内复制所必需的。ORC1突变唾液腺中细胞数量的减少与这一观点一致，即在胚胎发生期间检测不到的母体ORC1水平无法支持进一步的增殖。然而，这些细胞开始正常的内复制，并在没有ORC1合子合成的情况下达到>；1000C的最终倍体。对其他ORC成员的研究进一步支持了ORC的可有性，而双重停放的蛋白/CDT1和微小染色体维持蛋白显然是内复制所必需的，这意味着DNA复制的三种模式在启动的某些方面是相同的。这项研究深入了解了ORC在后生动物发育过程中的生理作用，并提出DNA复制启动在有丝分裂和内周期中受到不同的调控。
The origin recognition complex (ORC) is an essential component of the prereplication complex (pre-RC) in mitotic cell cycles. The role of ORC as a foundation to assemble the pre-RC is conserved from yeast to human. Furthermore, in metazoans ORC plays a key role in determining the timing of replication initiation and origin usage. in this report we have produced and analyzed a Drosophila orc1 allele to investigate the roles of ORC1 in three different modes of DNA replication during development. As expected, ORC1 is essential for mitotic replication and proliferation in brains and imaginal discs, as well as for gene amplification in ovarian follicle cells. Surprisingly, however, ORC1 is not required for endoreplication. Decreased cell number in orc1 mutant salivary glands is consistent with the idea that undetectable levels of maternal ORC1 during embryogenesis fail to support further proliferation. Nevertheless, these cells begin endoreplicating normally and reach a final ploidy of > 1000C in the absence of zygotic synthesis of ORC1. The dispensability of ORC is further supported by an examination of other ORC members, whereas Double-parked protein/Cdt1 and minichromosome maintenance proteins are apparently essential for endoreplication, implying that some aspects of initiation are shared among the three modes of DNA replication. This study provides insight into the physiologic roles of ORC during metazoan development and proposes that DNA replication initiation is governed differently in mitotic and endocycles.