芝麻开门：激活小鼠免疫球蛋白重链（Igh）基因座中的休眠复制起点。
Open sesame: activating dormant replication origins in the mouse immunoglobulin heavy chain (Igh) locus.
机构信息
Department of Biochemistry and New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, United States.
出版信息
Curr Opin Cell Biol. 2011 Jun;23(3):284-92. doi: 10.1016/j.ceb.2011.04.004. Epub 2011 May 14.
Abstract
Chromosomal DNA replication in mammals initiates from replication origins whose activity differs in accordance with cell type and differentiation state. In addition to origins that are active in unperturbed conditions, chromosomes also contain dormant origins that can become functional in response to certain genotoxic stress conditions. Improper regulation of origin usage can cause genomic instability leading to tumorigenesis. We review findings from recent single-molecule DNA fiber studies examining replication of the mouse immunoglobulin heavy chain (Igh) locus, in which origin activity over a 400kb region is subject to dramatic developmental regulation. Possible models are discussed to explain such differential origin usage, particularly during replication stress conditions that can activate dormant origins.
摘要
哺乳动物的染色体 DNA 复制从复制起点开始，其活性根据细胞类型和分化状态而有所不同。除了在未受干扰的条件下活跃的起点外，染色体还包含休眠起点，这些起点可以在某些遗传毒性应激条件下变得有功能。原点使用的不当调节会导致基因组不稳定性，从而导致肿瘤发生。我们回顾了最近的单分子 DNA 纤维研究的发现，这些研究检查了小鼠免疫球蛋白重链（Igh）基因座的复制，其中在 400kb 区域内的起点活性受到明显的发育调节。讨论了可能的模型来解释这种差异的原点使用，特别是在可以激活休眠原点的复制应激条件下。
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