结合功能基因组图的C. elegans的DNA损伤反应反应
Simon J Boulton1, Anton Gartner, Jérôme Reboul
1Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
概括
研究人员确定了新的DNA损伤反应 (DDR) 基因,这对于理解人类癌症至关重要. 这一发现利用了模型生物中的先进遗传映射,可能有助于未来的疾病研究.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 人类癌症通常是由DNA损伤反应 (DDR) 的中断引起的.
- 虽然已知许多DDR基因,但对新型基因的搜索仍在继续.
- 了解DDR对于推进癌症疗法至关重要.
研究的目的:
- 发现参与DNA损伤反应 (DDR) 的新基因.
- 为了确定人类癌症的新治疗点.
- 探索模型生物对人类疾病基因发现的实用性.
主要方法:
- 使用了蛋白质-蛋白质相互作用映射的综合策略.
- 在模型生物Caenorhabditis elegans中进行了大规模的表型分析.
- 综合功能基因组测绘方法.
主要成果:
- 鉴定了12名Caenorhabditis elegansDNA损伤反应 (DDR) 的正义学家.
- 发现了11个新的DDR基因.
- 发现了hBCL3的潜在正义基因,该基因与慢性淋巴细胞白血病有关.
结论:
- 在模型生物中功能性基因组测绘的综合方法有效地识别了DDR基因.
- 这一策略可以促进发现和描述与癌症有关的基因.
- 这些发现可能会扩展到与其他人类疾病有关的基因的识别.
相关概念视频
Nucleotide Excision Repair
Overview
Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
Base Excision Repair
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Base-pairing and DNA Repair
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
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...
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...


