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基因组组织促使染色体脆弱

Andres Canela¹, Yaakov Maman¹, Seolkyoung Jung²

¹Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA.

|July 25, 2017

概括

由CTCF和凝聚素结合的染色体环容易发生DNA双链断裂 (DSB). 这些断裂在很大程度上独立于转录或复制,发生在脆弱的部位,导致癌症相关的染色体重组.

科学领域:

基因组学
分子生物学
癌症生物学

背景情况:

CCCTC结合因子 (CTCF) 和凝聚素形成染色体循环,对基因组组织至关重要.
拓酶2B (TOP2B) 涉及到DNA双链断裂 (DSB) 的形成.
基因组重组与包括癌症在内的各种疾病有关.

研究的目的:

研究CTCF/凝聚环对TOP2B介导的DNA双链断裂 (DSB) 的脆弱性.
确定循环和染色体重排之间的关系.
评估DSB形成对转录,复制和细胞类型的依赖性.

主要方法:

对CTCF和凝聚性占用率的分析.
鉴定TOP2B介导的DNA分裂点.
对DSB位置的全基因组分析及其与拓域边界和断点集群的相关性.
对转录和复制依赖性的评估.

主要成果:

通过CTCF和凝聚素结合的进化保存的染色体循环易受TOP2B介导的DSB的影响.
改变CTCF/凝聚素结合的基因组多态性将分裂部位重定向到新的循环.
循环中的DSB在很大程度上独立于转录,复制和细胞类型.
DSB 发生在整个相间,在拓域边界附近,以及与癌症相关的断点集群.

结论:

染色体循环作为脆弱的位置,产生DSB.
这些DSB有助于染色体重组,特别是癌症中观察到的染色体重组.
循环的DSB形成是一个基本的过程,基本上与活跃的转录或复制无关.

关键词:

DNA 断裂断点集群地区癌症脆弱的地方基因组不稳定性一种类型拓相关的域转移情况

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