BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges
BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges
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DOI：
10.1038/sj.emboj.7601777
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发表时间：
2007-07-25
期刊：
影响因子：
11.4
通讯作者：
Hickson, Ian D.
中科院分区：
文献类型：
--
作者：
Chan, Kok-Lung;North, Phillip S.;Hickson, Ian D.
BLM的突变导致布卢姆综合征，这是一种与癌症易感性和染色体不稳定性相关的疾病。我们研究了BLM是否在确保人类细胞中染色体分离的可靠性方面发挥作用。我们发现，BLM缺陷的细胞表现出更高的频率后期桥和落后的染色质比同基因校正的衍生物，异位表达的BLM蛋白。在进行有丝分裂的正常细胞中，BLM蛋白定位于后期桥，在那里它与其细胞伴侣拓扑异构酶IIIa和hRMI 1（BLAP 75）共定位。使用BLM染色作为标记，我们已经确定了一类超细的DNA桥在后期，这是令人惊讶的普遍存在于后期人口的正常人类细胞。这些所谓的BLM-DNA桥，也为PICH蛋白染色，经常连接着丝粒位点，并在缺乏BLM的细胞中以升高的频率存在。根据这些结果，我们提出，姐妹染色单体分离往往是不完整的人类细胞，即使发病后的后期。我们提出了一个模型的行动，BLM在确保完整的姐妹染色单体脱连锁在后期。
Mutations in BLM cause Bloom's syndrome, a disorder associated with cancer predisposition and chromosomal instability. We investigated whether BLM plays a role in ensuring the faithful chromosome segregation in human cells. We show that BLM-defective cells display a higher frequency of anaphase bridges and lagging chromatin than do isogenic corrected derivatives that eptopically express the BLM protein. In normal cells undergoing mitosis, BLM protein localizes to anaphase bridges, where it colocalizes with its cellular partners, topoisomerase IIIa and hRMI1 (BLAP75). Using BLM staining as a marker, we have identified a class of ultrafine DNA bridges in anaphase that are surprisingly prevalent in the anaphase population of normal human cells. These so-called BLM-DNA bridges, which also stain for the PICH protein, frequently link centromeric loci, and are present at an elevated frequency in cells lacking BLM. On the basis of these results, we propose that sister-chromatid disjunction is often incomplete in human cells even after the onset of anaphase. We present a model for the action of BLM in ensuring complete sister chromatid decatenation in anaphase.