McNulty Shannon M, Sullivan Beth A
Department of Molecular Genetics and Microbiology, Duke University Medical Center, DUMC 3054, Durham, NC, 27710, USA.
Division of Human Genetics, Duke University Medical Center, DUMC 3054, Durham, NC, 27710, USA.
Prog Mol Subcell Biol. 2017;56:233-255. doi: 10.1007/978-3-319-58592-5_10.
Centromere function is essential for genome stability and chromosome inheritance. Typically, each chromosome has a single locus that consistently serves as the site of centromere formation and kinetochore assembly. Decades of research have defined the DNA sequence and protein components of functional centromeres, and the interdependencies of specific protein complexes for proper centromere assembly. Less is known about how centromeres are disassembled or functionally silenced. Centromere silencing, or inactivation, is particularly relevant in the cases of dicentric chromosomes that occur via genome rearrangements that place two centromeres on the same chromosome. Dicentrics are usually unstable unless one centromere is inactivated, thereby allowing the structurally dicentric chromosome to behave like one of the monocentric, endogenous chromosomes. The molecular basis for centromere inactivation is not well understood, although studies in model organisms and in humans suggest that both genomic and epigenetic mechanisms are involved. In this chapter, we review recent studies using synthetic chromosomes and engineered or induced dicentrics from various organisms to define the molecular processes that are involved in the complex process of centromere inactivation.
着丝粒功能对于基因组稳定性和染色体遗传至关重要。通常，每条染色体都有一个单一的位点，该位点始终作为着丝粒形成和动粒组装的位点。数十年的研究已经明确了功能性着丝粒的DNA序列和蛋白质成分，以及特定蛋白质复合物对于正确着丝粒组装的相互依赖性。关于着丝粒如何解聚或功能沉默，人们了解得较少。着丝粒沉默或失活在通过基因组重排产生的双着丝粒染色体的情况下尤为重要，这种重排会在同一条染色体上放置两个着丝粒。双着丝粒通常不稳定，除非一个着丝粒失活，从而使结构上的双着丝粒染色体表现得像单着丝粒的内源染色体之一。尽管在模式生物和人类中的研究表明基因组和表观遗传机制都参与其中，但着丝粒失活的分子基础尚未得到很好的理解。在本章中，我们综述了最近使用合成染色体以及来自各种生物体的工程化或诱导性双着丝粒进行的研究，以确定参与着丝粒失活复杂过程的分子过程。
