The origin recognition complex in human diseases.
The origin recognition complex in human diseases.
复制标题
人类疾病中的起源识别综合体。
DOI：
10.1042/bsr20130036
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发表时间：
2013-06-11
影响因子：
4
通讯作者：
Shen Z
中科院分区：
文献类型：
--
作者：
Shen Z
ORC（起源识别复合物）充当 pre-RC（预复制复合物）组装和随后 DNA 复制的引发剂。连同其许多非复制功能，ORC 是各种细胞过程的关键调节器。值得注意的是，许多报告将 ORC 与多种人类疾病联系起来，包括 MGS（迈尔-戈林综合征）、EBV（爱泼斯坦-巴尔病毒）感染性疾病、美洲锥虫病和非洲锥虫病。然而，许多潜在的分子机制仍不清楚。在这些遗传性疾病中，ORC 的突变会改变其功能并导致表型失调；而在一些病原体引起的症状中，宿主 ORC 和类古菌 ORC 被这些生物体利用来维持自己的基因组。在这篇综述中，我提供了与 ORC 相关的人类疾病的详细例子，并总结了有关 ORC 如何参与和/或失调的当前发现。我进一步讨论如何将这些发现推广为模型系统，然后将其应用于阐明其他相关疾病并揭示开发有效疗法的潜在靶标。
ORC (origin recognition complex) serves as the initiator for the assembly of the pre-RC (pre-replication complex) and the subsequent DNA replication. Together with many of its non-replication functions, ORC is a pivotal regulator of various cellular processes. Notably, a number of reports connect ORC to numerous human diseases, including MGS (Meier–Gorlin syndrome), EBV (Epstein–Barr virus)-infected diseases, American trypanosomiasis and African trypanosomiasis. However, much of the underlying molecular mechanism remains unclear. In those genetic diseases, mutations in ORC alter its function and lead to the dysregulated phenotypes; whereas in some pathogen-induced symptoms, host ORC and archaeal-like ORC are exploited by these organisms to maintain their own genomes. In this review, I provide detailed examples of ORC-related human diseases, and summarize the current findings on how ORC is involved and/or dysregulated. I further discuss how these discoveries can be generalized as model systems, which can then be applied to elucidating other related diseases and revealing potential targets for developing effective therapies.