相关实验视频

Updated: May 5, 2026

Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae

Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae

Published on: September 23, 2011

DNA损伤定义了B淋巴细胞中经常发生的染色体转位的部位

Ofir Hakim¹, Wolfgang Resch, Arito Yamane

¹Laboratory of Receptor Biology and Gene Expression, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.

|February 9, 2012

概括

癌症中的染色体转位是由核组织或DNA损伤引起的. 非向转位反映了核接触,而DNA断裂则驱动了B细胞恶性瘤中的反复转位.

科学领域:

遗传学是一个遗传学.
癌症生物学癌症生物学
分子生物学分子生物学

背景情况:

经常发生的染色体转位是许多癌症的标志,包括血液和固体瘤.
这些转位的起源受到辩论,提出的机制包括随机重新排列,有针对性的DNA损伤和转位伙伴之间频繁的核相互作用.
这些因素的相对贡献尚未得到广泛的量化.

研究的目的:

调查核结构和DNA损伤频率在染色体转位的起源中的作用.
在模型系统中同时测量这些参数,以了解转位起源.
确定核组织和DNA损伤如何影响转位模式.

主要方法:

培养的小鼠B淋巴细胞被用作模型系统.
核架构 (基因之间的接触频率) 和DNA损伤 (通过复制蛋白A积累来衡量) 被同时评估.
确定了特定基因 (Igh,Myc) 和其他基因之间的转位的频率.

主要成果:

在没有向DNA损伤的情况下,Igh或Myc等基因与其他基因之间的转位频率与它们的核接触频率直接相关.
当复发的局部导向DNA损伤存在时,转位频率与DNA断裂形成的速度成比例.
这表明非目标重排是由核组织控制的,而DNA断裂则决定了反复转位的位置和频率.

结论:

核组织在非向的染色体转位中起着关键作用.
DNA 断裂形成是反复转位的位置和频率的主要驱动因素.
这些发现对了解B细胞恶性瘤和潜在的其他由转位驱动的癌症背后的机制有影响.

更多相关视频

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Published on: August 19, 2014

Dual Immunofluorescence of γH2AX and 53BP1 in Human Peripheral Lymphocytes

Dual Immunofluorescence of γH2AX and 53BP1 in Human Peripheral Lymphocytes

Published on: July 14, 2023

相关概念视频

Translesion DNA Polymerases

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...

Fixing Double-strand Breaks

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...

Homologous Recombination

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...

Conservative Site-specific Recombination and Phase Variation

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...

Nucleotide Excision Repair

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

Crossing Over

Crossing Over

Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...