染色体灾难涉及复制机制,产生复杂的基因组重新排列
Pengfei Liu1, Ayelet Erez, Sandesh C Sreenath Nagamani
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Cell
|September 20, 2011
概括
复杂的基因组重组 (CGRs) 类似于癌症染色体,表明共享的DNA修复机制. 这些事件涉及多个副本数量变化和广泛的基因组变化,突出了基本的DNA代谢.
科学领域:
- 遗传学 是一个遗传学.
- 基因组不稳定性 基因组不稳定性
- 分子生物学分子生物学
背景情况:
- 复杂的基因组重组 (CGR) 具有多个断点结的特征.
- 在癌症中观察到的Chromothripsis是一种在单一事件中发生大规模基因组重组的现象.
研究的目的:
- 调查宪法获得的CGR和癌症染色体的相似之处.
- 阐明CGR和染色体的机械基础.
主要方法:
- 分析了17个具有CGR的病例.
- 对于副本数量变化的数组比较基因组杂交 (aCGH).
- 断点测序以识别结点特征. 断点测序用于识别结点特征.
主要成果:
- CGR 呈现出多个副本数量变化 (删除,重复,三重复) 和广泛的转移/反转.
- 断点分析揭示了小模板插入和微同质性,表明复制过程.
- 观察到CGRs和癌症染色体的基因组特征有显著的重叠.
结论:
- 宪法获得的CGR与癌症染色体的机制相似.
- 这些染色体灾难性事件可能反映了基本的DNA代谢过程.
- 了解这些机制对于基因组疾病和癌症研究至关重要.
相关概念视频
Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Fixing Double-strand Breaks
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Fixing Double-strand Breaks
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...


