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Replication, checkpoint suppression and structure of centromeric DNA

机译:着丝粒DNA的复制,检查点抑制和结构

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Human centromeres contain large amounts of repetitive DNA sequences known as a satellite DNA, which can be difficult to replicate and whose functional role is unclear. Recently, we have characterized protein composition, structural organization and checkpoint response to stalled replication forks of centromeric chromatin reconstituted in Xenopus laevis egg extract. We showed that centromeric DNA has high affinity for SMC2-4 subunits of condensins and for CENP-A, it is enriched for DNA repair factors and suppresses the ATR checkpoint to ensure its efficient replication. We also showed that centromeric chromatin forms condensins enriched and topologically constrained DNA loops, which likely contribute to the overall structure of the centromere. These findings have important implications on how chromosomes are organized and genome stability is maintained in mammalian cells.
机译:人类着丝粒包含大量重复的DNA序列,称为卫星DNA,可能难以复制,其功能作用尚不清楚。最近,我们表征了非洲爪蟾卵提取物中重构的着丝粒染色质的停滞复制叉的蛋白质组成,结构组织和检查点响应。我们显示着丝粒DNA对凝缩蛋白的SMC2-4亚基和CENP-A具有高亲和力,富含DNA修复因子并抑制ATR检查点以确保其有效复制。我们还表明,着丝粒染色质形成浓缩凝集素和拓扑约束DNA环,这可能有助于着丝粒的整体结构。这些发现对哺乳动物细胞中染色体的组织方式和基因组稳定性的维持具有重要意义。

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