Mechanisms driving chromosomal translocations: lost in time and space.

Mechanisms driving chromosomal translocations: lost in time and space.
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驱动染色体易位的机制:迷失在时间和空间中。

DOI:
10.1038/s41388-021-01856-9
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发表时间:
2021-06
期刊:
影响因子:
8
通讯作者:
Nussenzweig A
Nussenzweig A
中科院分区:
医学1区
文献类型:
--
作者:
Ramsden DA;Nussenzweig A

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当一个染色体断裂的末端错误地连接到另一个染色体断裂的末端时,就会发生易位。由于易位可导致发育性疾病和癌症,因此了解导致这些染色体重排的机制非常重要。我们回顾了来源的特性和细胞对染色体断裂的反应如何在同一时刻促进多个染色体断裂的积累。我们还讨论了染色体断裂位置的重要作用;染色体断裂在染色质内和细胞核内的位置如何影响易位潜力,以及染色体断裂的迁移率改变的影响。一个共同的主题,在工作中解决时间和空间的贡献易位是,有不缺乏的例子的因素,促进易位在一个上下文中,但没有影响或相反的影响在另一个。因此,未来关于易位机制的工作的一个明确信息是,与正常的DNA代谢途径不同,它不容易被建模为一个简单的线性途径,无论不同的细胞环境如何,都要遵循这个途径。
Translocations arise when an end of one chromosome break is mistakenly joined to an end from a different chromosome break. Since translocations can lead to developmental disease and cancer, it is important to understand the mechanisms leading these chromosome rearrangements. We review how characteristics of the sources and the cellular responses to chromosome breaks contribute to the accumulation of multiple chromosome breaks at the same moment in time. We also discuss the important role for chromosome break location; how translocation potential is impacted by the location of chromosome breaks both within chromatin and within the nucleus, as well as the effect of altered mobility of chromosome breaks. A common theme in work addressing both temporal and spatial contributions to translocation is that there is no shortage of examples of factors that promote translocation in one context, but have no impact or the opposite impact in another. Accordingly, a clear message for future work on translocation mechanism is that unlike normal DNA metabolic pathways, it isn’t easily modeled as a simple, linear pathway that is uniformly followed regardless of differing cellular contexts.
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