Chromosome Segregation Errors as a Cause of DNA Damage and Structural Chromosome Aberrations
Chromosome Segregation Errors as a Cause of DNA Damage and Structural Chromosome Aberrations
复制标题
DOI：
10.1126/science.1210214
复制
发表时间：
2011-09-30
期刊：
影响因子：
56.9
通讯作者：
Medema, Rene H.
中科院分区：
文献类型：
--
作者：
Janssen, Aniek;van der Burg, Marja;Medema, Rene H.
各种类型的染色体畸变，包括数量（非整倍性）和结构（例如，例如，在一个实施例中，易位、缺失）通常在人类肿瘤中发现并且与肿瘤发生有关。非整倍性是有丝分裂中染色体分离错误的直接结果，而结构畸变是由不正确修复的DNA断裂引起的。在这里，我们证明了染色体分离错误也可以导致染色体结构畸变。错误分离的染色体在胞质分裂期间经常受损，在涉及ATM、Chk2和p53的相应子细胞中触发DNA双链断裂反应。我们发现，这些双链断裂可能导致子细胞中的不平衡易位。我们的数据表明，分离错误可以导致易位，并提供了深入了解肿瘤发生中的全染色体不稳定性的作用。
Various types of chromosomal aberrations, including numerical (aneuploidy) and structural (e. g., translocations, deletions), are commonly found in human tumors and are linked to tumorigenesis. Aneuploidy is a direct consequence of chromosome segregation errors in mitosis, whereas structural aberrations are caused by improperly repaired DNA breaks. Here, we demonstrate that chromosome segregation errors can also result in structural chromosome aberrations. Chromosomes that missegregate are frequently damaged during cytokinesis, triggering a DNA double-strand break response in the respective daughter cells involving ATM, Chk2, and p53. We show that these double-strand breaks can lead to unbalanced translocations in the daughter cells. Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis.