Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites
Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites
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DOI：
10.1073/pnas.0506497102
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发表时间：
2005-12-13
影响因子：
11.1
通讯作者：
Debatisse, M
中科院分区：
文献类型：
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作者：
El Achkar, E;Gerbault-Seureau, M;Debatisse, M
各种研究表明，染色体重排驱动肿瘤进展与称为常见脆性位点的位点断裂之间存在密切关系。大多数这些网站诱导后扰动的复制动力学，特别是aphidicolin治疗。我们已经将这些网站的大部分映射到R和G带的界面，这对以前将aphidicolin敏感网站分配到R带提出了质疑。这一观察结果表明，它们中的大多数对应于确保早期和晚期复制域之间的过渡的基因座。我们发现，在细胞周期的任何阶段触发染色体凝聚，但不明显损害复制的calyculin A，诱导G（2）期而不是G（1）期处理的人淋巴细胞的染色体损伤。我们证明，这些病变共定位与aphidicolin治疗引起的。因此，无论aphidicolin延迟复制还是calyculin A促进缩合，常见的脆性位点稳定性都受到损害。我们还发现，在经历未受干扰的S期的细胞中，它们的复制和/或复制相关的染色质重组的完成发生在整个沿着G（2）期，这可以解释它们在细胞周期的这个阶段中在calyculin A处理后不能正确地浓缩。
Various studies suggest a tight relationship between chromosome rearrangements driving tumor progression and breaks at loci called common fragile sites. Most of these sites are induced after perturbation of the replication dynamics, notably by aphidicolin treatment. We have mapped the majority of these sites to the interface of R and G bands, which calls into question the previous assignment of aphidicolin-sensitive sites to R bands. This observation suggests that most of them correspond to loci that ensure the transition between early and late replicating domains. We show that calyculin A, which triggers chromosome condensation at any phase of the cell cycle but does not markedly impair replication, induces damage in the chromosomes of human lymphocytes treated in G(2) but not in G(1) phase. We demonstrate that these lesions colocalize with those induced by aphidicolin treatment. Hence, common fragile site stability is compromised, whether aphidicolin delays replication or calyculin A advances condensation. We also show that, in cells that go through an unperturbed S phase, completion of their replication and/or replication-associated chromatin reorganization occur all along the G(2) phase, which may explain their inability to condense properly after calyculin A treatment during this phase of the cell cycle.