端粒功能障碍增加了突变率和基因组不稳定性
J A Hackett1, D M Feldser, C W Greider
1Predoctoral Training Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|August 18, 2001
概括
端粒功能障碍是由端粒酶缺乏引起的,显著增加突变率和遗传不稳定性. 这项在酵母中的研究揭示了端粒酶的存在.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 端粒功能障碍与小鼠的瘤发病率增加和遗传不稳定性有关.
- 端粒酶在维持端粒长度和稳定性方面发挥着至关重要的作用.
研究的目的:
- 直接调查端粒功能障碍与遗传不稳定之间的联系.
- 为了确定端粒酶缺失对Saccharomyces cerevisiae中的突变率的影响.
主要方法:
- 评估est1Delta酵母菌株CAN1基因中的突变率,这些酵母菌株具有功能障碍的端粒.
- 分析突变的类型,包括终端缺失和染色体融合.
- 研究端粒修复机制,例如断裂诱导的复制.
主要成果:
- 突变率在具有功能障碍的端粒的 est1Delta 菌株中增加了 10 到 100 倍.
- 突变率的增加主要是由于末端删除的频率更高.
- 染色体融合和复杂重排的证据表明,有断裂-融合-桥梁机制和其他不稳定路径.
结论:
- 端粒酶缺失导致显著的染色体不稳定.
- 端粒功能障碍直接导致遗传不稳定.
- 端粒酶作为染色体不稳定的抑制剂.
相关概念视频
Dihybrid Crosses
Overview
Mismatch Repair
Overview
Mutation, Gene Flow, and Genetic Drift
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
Trihybrid Crosses
Trihybrid Crosses
Some of Mendel’s crosses examined three pairs of contrasting characteristics. Such a cross is called a trihybrid cross. A trihybrid cross is a combination of three individual monohybrid crosses. For example, plant height (tall vs. short), seed shape (round vs. wrinkled), and seed color (yellow vs. green).
The F1 generation plants of a trihybrid cross are heterozygous for all three traits and produce eight gametes. Upon self-fertilization, these gametes have an equal chance to...
Some of Mendel’s crosses examined three pairs of contrasting characteristics. Such a cross is called a trihybrid cross. A trihybrid cross is a combination of three individual monohybrid crosses. For example, plant height (tall vs. short), seed shape (round vs. wrinkled), and seed color (yellow vs. green).
The F1 generation plants of a trihybrid cross are heterozygous for all three traits and produce eight gametes. Upon self-fertilization, these gametes have an equal chance to...
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.
Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...


