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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The origin recognition complex is dispensable for endoreplication in Drosophila
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The origin recognition complex is dispensable for endoreplication in Drosophila

机译：起源识别复合物对于果蝇的内复制是必不可少的

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摘要

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.
机译：起源识别复合体（ORC）是有丝分裂细胞周期中复制前复合体（pre-RC）的重要组成部分。从酵母到人，保守了ORC作为组装pre-RC的基础的作用。此外，在后生动物中，ORC在确定复制起始时间和来源使用方面起着关键作用。在本报告中，我们产生并分析了果蝇orc1等位基因，以研究ORC1在发育过程中DNA复制的三种不同模式中的作用。如预期的那样，ORC1对于大脑和假想椎间盘的有丝分裂复制和增殖以及卵巢卵泡细胞的基因扩增至关重要。但是，令人惊讶的是，内复制不需要ORC1。 orc1突变唾液腺中细胞数量的减少与这样的想法是一致的，即在胚胎发生过程中无法检测到的母亲ORC1的水平不能支持进一步的增殖。然而，这些细胞在没有合酶合成ORC1的情况下正常开始内复制，并达到＞ 1000℃的最终倍性。通过检查其他ORC成员进一步支持了ORC的可分配性，而双重停放蛋白/ Cdt1和微染色体维持蛋白显然对于内复制至关重要，这意味着起始的某些方面在DNA复制的三种模式之间共享。这项研究提供了对后生动物发育过程中ORC的生理作用的见解，并提出在有丝分裂和内周期中，DNA复制的起始调控是不同的。

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