Delayed replication timing leads to delayed mitotic chromosome condensation and chromosomal instability of chromosome translocations
Delayed replication timing leads to delayed mitotic chromosome condensation and chromosomal instability of chromosome translocations
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DOI：
10.1073/pnas.241355098
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发表时间：
2001-11-06
影响因子：
11.1
通讯作者：
Thayer, M
中科院分区：
文献类型：
--
作者：
Smith, L;Plug, A;Thayer, M
染色体重排几乎存在于所有类型的人类癌症中。我们发现某些染色体易位显示有丝分裂染色体凝结的延迟，这与组蛋白 H3 有丝分裂特异性磷酸化的延迟相关。有丝分裂浓缩的延迟先于染色体复制的起始和完成的延迟。此外，具有这种表型的染色体参与许多二次易位和重排。在七个肿瘤衍生细胞系中的五个和十三个原发性肿瘤样本中的五个中检测到具有这种表型的染色体。这些数据表明，肿瘤细胞中发现的某些染色体重排导致整个染色体的复制时间显着延迟，随后导致有丝分裂染色体凝集延迟，并最终导致染色体不稳定。
Chromosomal rearrangements are found in virtually all types of human cancers. We show that certain chromosome translocations display a delay in mitotic chromosome condensation that is associated with a delay in the mitosis-specific phosphorylation of histone H3. This delay in mitotic condensation is preceded by a delay in both the initiation as well as the completion of chromosome replication. in addition, chromosomes with this phenotype participate in numerous secondary translocations and rearrangements. Chromosomes with this phenotype were detected in five of seven tumor-derived cell lines and in five of thirteen primary tumor samples. These data suggest that certain chromosomal rearrangements found in tumor cells cause a significant delay in replication timing of the entire chromosome that subsequently results in delayed mitotic chromosome condensation and ultimately in chromosomal instability.