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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus
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c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus

机译：c-Myc通过端粒和相间核中的染色体重塑诱导染色体重排

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摘要

in previous work, we showed that telomeres of normal cells are organized within the 3D space of the interphase nucleus in a nonoverlapping and cell cycle-dependent manner. This order is distorted in tumor cell nuclei where telomeres are found in close association forming aggregates of various numbers and sizes. Here we show that c-Myc overexpression induces telomeric aggregations in the interphase nucleus. Directly proportional to the duration of c-Myc deregulation, we observe three or five cycles of telomeric aggregate formation in interphase nuclei. These cycles reflect the onset and propagation of breakage-bridge-fusion cycles that are initiated by end-to-end telomeric fusions of chromosomes. Subsequent to initial chromosomal breakages, new fusions follow and the breakage-bridge-fusion cycles continue. During this time, nonreciprocal translocations are generated. c-Myc-dependent remodeling of the organization of telomeres thus precedes the onset of genomic instability and subsequently leads to chromosomal rearrangements. Our findings reveal that c-Myc possesses the ability to structurally modify chromosomes through telomeric fusions, thereby reorganizing the genetic information.
机译：在以前的工作中，我们显示正常细胞的端粒以非重叠且依赖细胞周期的方式组织在相间核的3D空间内。该顺序在肿瘤细胞核中扭曲，其中端粒紧密结合，形成各种数量和大小的聚集体。在这里，我们显示c-Myc过表达在相间核中诱导端粒聚集。与c-Myc失调的持续时间成正比，我们观察到相间核中端粒聚集体形成的三个或五个周期。这些循环反映了由端对端染色体端粒融合引发的断裂桥融合循环的发生和传播。在最初的染色体断裂之后，出现新的融合，并且断裂-桥-融合循环继续进行。在这段时间内，产生了不可逆的易位。因此，端粒的依赖c-Myc的重塑在基因组不稳定发生之前，并随后导致染色体重排。我们的发现表明c-Myc具有通过端粒融合在结构上修饰染色体的能力，从而重组了遗传信息。

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