在DNA损伤反应中,预位性BID的作用
Sandra S Zinkel1, Kristen E Hurov, Christy Ong
1Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. sandra.zinkel@vanderbilt.edu
Cell
|August 27, 2005
概括
蛋白BID是细胞死亡的关键调节者,它通过在S相内DNA损伤检查点中发挥作用来意外地保持基因组完整性,这与其已知的亲细胞亡功能不同.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- BCL-2家族调节了亡,像BID这样的BH3-only蛋白质充当了关键的哨兵.
- 之前的研究将BH3-only BID与骨髓质平衡和抑制白血病发生联系起来.
- 在小鼠中,两位数缺陷导致染色体异常和骨髓增殖性疾病.
研究的目的:
- 阐明BID在维护基因组完整性方面的作用.
- 为了研究BID在DNA损伤反应途径中的功能.
- 确定BID在细胞命运决定中的非亡作用机制.
主要方法:
- 对投标缺陷小鼠模型的分析.
- 在DNA损伤后对S阶段内检查点的调查.
- 通过ATM激酶对BID酸化的评估.
主要成果:
- 在S相内DNA损伤检查点中,BID起着意想不到的作用.
- 这一职能与BID已建立的亲子亡活动不同.
- 通过ATM的BID酸化调解其在保护基因组完整性方面的作用.
结论:
- 通过其参与S期内检查点,BID对于保持基因组稳定性至关重要.
- BID的功能超越了细胞亡,将其与DNA损伤反应联系起来.
- 这些发现揭示了一种新的机制,即BID在DNA损伤后影响细胞命运决定.
相关概念视频
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.
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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...
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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...
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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...


