一个向序列将DNA甲基转移酶引导到哺乳动物核中的DNA复制位点
H Leonhardt1, A W Page, H U Weier
1Department of Anatomy and Cellular Biology, Harvard Medical School, Boston, Massachusetts 02115.
Cell
|November 27, 1992
概括
DNA甲基转移酶 (MTase) 在DNA合成过程中准复制分叉. 一个新的N-终端序列指导这种细胞周期特定的局部化,对于维持基因组甲基化模式至关重要.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 基因组甲基化模式对于哺乳动物基因组调节至关重要.
- 复制后甲基化确保了DNA复制过程中这些模式的继承.
- 在这个过程中,DNA甲基转移酶 (MTase) 活性是必不可少的.
研究的目的:
- 为了研究DNA甲基转移酶 (MTase) 的细胞周期局部化.
- 确定MTase与复制焦点相关联的机制.
- 在DNAMTase中描述一种新的准序列.
主要方法:
- 免疫光显微镜可视化细胞周期期间的MTase局部化.
- 对DNAMTase-beta-galactosidase融合蛋白的分析.
- 位点定向的突变发生,以删除或转移假定的向序列.
主要成果:
- 在S阶段,DNA MTase定位到复制焦点,并在非S阶段细胞中表现出扩散的核等离子分布.
- 在DNAMTase的N端附近的一个新的准序列调解了与复制焦点的关联.
- 这种向序列独立于酶活性,并赋予异质蛋白质细胞周期依赖的局部化.
结论:
- 一个特定的N端序列在S阶段将DNAMTase引导到复制部位.
- 这种局部化机制对于在DNA复制过程中保持表观遗传忠实性至关重要.
- 鉴定到的向序列为以细胞周期依赖的方式研究蛋白质定位提供了一个新的工具.
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