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Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis
Trends in Cell Biology ( IF 19.0 ) Pub Date : 2017-09-09 , DOI: 10.1016/j.tcb.2017.08.005
Peter Ly , Don W. Cleveland

Cancer genome sequencing has identified chromothripsis, a complex class of structural genomic rearrangements involving the apparent shattering of an individual chromosome into tens to hundreds of fragments. An initial error during mitosis, producing either chromosome mis-segregation into a micronucleus or chromatin bridge interconnecting two daughter cells, can trigger the catastrophic pulverization of the spatially isolated chromosome. The resultant chromosomal fragments are religated in random order by DNA double-strand break repair during the subsequent interphase. Chromothripsis scars the cancer genome with localized DNA rearrangements that frequently generate extensive copy number alterations, oncogenic gene fusion products, and/or tumor suppressor gene inactivation. Here we review emerging mechanisms underlying chromothripsis with a focus on the contribution of cell division errors caused by centromere dysfunction.



中文翻译:

灾难后重建染色体:拟除虫菊酯的新机制

癌症基因组测序已鉴定出染色体脱色,这是一类复杂的结构基因组重排,涉及单个染色体的明显破碎成数十至数百个片段。有丝分裂期间的初始错误会导致染色体错误分离成微核或连接两个子细胞的染色质桥,从而可能引发空间分离的染色体的灾难性粉碎。所得染色体片段在随后的中间阶段通过DNA双链断裂修复以随机顺序重新连接。淋菌病通过局部DNA重排使癌症基因组受惊,DNA重排经常产生大量的拷贝数改变,致癌基因融合产物和/或肿瘤抑制基因失活。

更新日期:2017-09-09
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