着丝粒核小体结构研究进展

着丝粒是构成真核生物染色体的必需元件。在细胞有丝分裂或减数分裂时,微管通过动粒与染色体着丝粒连接,参与细胞分裂的染色体分离与分配过程,使染色体平均分配到子细胞中。构成着丝粒的基本单位是着丝粒特异的核小体,与常规核小体不同的是着丝粒核小体中的组蛋白H3被其变种——着丝粒组蛋白H3所替换。最近几年,着丝粒核小体的结构成为细胞生物学研究的热点之一。该文综述了最近在多种真核生物研究中,通过体外和体内实验,提出的着丝粒核小体结构的八聚体、六聚体、同型四聚体以及半八聚体模型,并对着丝粒核小体结构的动态模型与功能的关系进行了探讨。     

植物功能着丝粒DNA研究进展

着丝粒（centromere）是真核生物染色体的重要功能结构。在细胞有丝分裂和减数分裂过程中,着丝粒通过招募动粒蛋白行使功能,保障染色体正确分离和传递。真核生物中,含有着丝粒特异组蛋白的CenH3区域被定义为功能着丝粒区,即真正意义上的着丝粒。近年来,借助染色质免疫沉淀技术,人们对功能着丝粒DNA开展了深入研究,揭示其组成、结构及演化特征,并发现功能着丝粒区存在具有转录活性的基因,且部分基因具有重要生物学功能。由于存在大量重复DNA,着丝粒演化之谜一直未能完全揭示。对植物功能着丝粒DNA序列研究进展进行了概述,并重点阐述了着丝粒重复DNA研究的新方法和新进展,以期为深入开展相关研究提供借鉴。     

着丝粒和动粒

真核生物的染色体具有用于将2条臂分开的着丝粒结构.在着丝粒的外侧,具有与纺锤体直接相连的结构——动粒.着丝粒是一个复杂的DNA-蛋白质复合结构,是真核生物细胞分裂的轮毂;动粒是着丝粒在行使轮毂(调控中心)作用时赖以与细胞分裂“拉力器”(纺锤体)相啮合的动力支撑点.     

小鼠富集着丝粒DNA在小鼠减数分裂粗线期染色体上的原位杂交

本工作用Ｈｏｅｃｈｓｔ ３３２５８及着丝粒特异抗体间接免疫荧光法显示的小鼠粗线期染色体主缢痕区,与以小鼠富集着丝粒ＤＮＡ为探针在粗线期染色体上的原位杂交主缢痕区作了比较。发现ＳＦＡ ＤＮＡ探针不仅杂交于全部常染色体联会复合体上的着线粒区,并且杂交于着丝粒周围的异染色质区;而且,也杂交于Ｘ,Ｙ染色体的着丝粒区。由此结论：此富集ＳＦＡ ＤＮＡ中含有全套常染色体及Ｘ,Ｙ染色体的ＳＦＡ ＤＮＡ。     

着丝粒横裂和着丝粒并合及其在高等植物染色体进化中的意义

本文讨论了着丝粒横裂和并合及其在高等植物染色体进化中的意义。着丝粒横裂和着丝粒并合是两个矛盾又辩证统一的过程,是染色体的基本变异形式之一,它们同时影响着植物类群的染色体基数、核型对称性、连锁关系、交叉频率和位点等细胞遗传学的重要方面.从而在高等植物染色体进化中起着重要作用,着丝粒和端粒的复制模型为着丝粒的横裂与并合提供了可能的机理,但尚待直接的生物化学证据的证实,原始基数的确定是判别着丝粒横裂与并合的关键。     

人类染色体着丝粒蛋白研究进展

人类染色体着丝粒蛋白研究进展朱学良（中国科学技术大学生物系合肥２３００２６）１着丝粒、动植和着丝粒一动粒复合体细胞分裂过程中姐妹染色体的均等分离是一切生物赖以生长和繁殖的基础之一。着丝粒（ｃｅｎｔｒｏｍｅｒｅ）是染色体位于初缢痕的部分,在光学显微镜下...     

玉米新着丝粒形成及其表观遗传学

<正>着丝粒是染色体的重要组成部分,功能保守,在细胞分裂过程中确保染色体准确分离。在着丝粒区域的核小体中,有一类组蛋白H3的变异体,在植物中称为CENH3,在动物中称为CENP-A;同时植物中含有在第133位苏氨酸发生磷酸化的组蛋白H2A,这两类组蛋白是活性着丝粒的表观遗传学标记。着丝粒区域的DNA序列经历了高度的进化。除     

恶性血液病中着丝粒和着丝粒周染色体重排的研究进展

用染色体特异的卫星DNA探针染色体荧光原位杂交（FISH）分析恶性血液病,发现着丝粒和着丝粒周染色体的重排并非罕见。分子生物学技术和基因组计划的发展,促进了对异染色质分子本质的研究。本就着丝粒和着丝粒周异染色质的分子结构及其重排机制作一综述。     

植物着丝粒结构及进化的研究进展

植物着丝粒是染色体重要结构域,介导动粒装配。不同物种间着丝粒重复序列快速趋异进化,着丝粒功能保守,确保有丝分裂和减数分裂过程中染色体正确分离和准确传递。伴随染色质免疫共沉淀技术(Chromatin immunoprecipitation, ChIP)、ChIP 与高密度芯片相结合技术(ChIP-chip)、ChIP 与高通量测序相结合技术(ChIP-seq)的应用,植物着丝粒研究获得里程碑式进展:某些模式植物着丝粒DNA 序列、蛋白质结构、功能获得大量新认识;着丝粒基本蛋白质组蛋白H3 被用来界定着丝粒大小和边界;某些非着丝粒区域被激活为新着丝粒,在世代传递中保持稳定性。本文对植物着丝粒结构、功能、进化研究进行了综述,并探讨了植物着丝粒研究存在的问题。     

着丝粒区域DNA的研究进展

着丝粒是染色体的重要结构,在真核生物的细胞分裂中负责染色体的分裂分离。近年来对着丝粒的研究已经成为遗传学的一个热点。本文对着丝粒DNA的重复序列、着丝粒区域的基因及着丝粒的形成机制等作了简要的介绍。     

An overview of plant centromeres

The centromere is a defining region that mediates chromosome attachment to kinetochore microtubules and proper segregation of the sister chromatids. Intriguingly, satellite DNA and centromeric retrotransposon as major DNA constituents of centromere showed baffling diversification and species-specific. However, the key kinetochore proteins are conserved in both plants and animals, particularly the centromere-specific histone H3-1ike protein （CENH3） in all functional centromeres. Recent studies have highlighted the importance of epigenetic mechanisms in the establishment and maintenance of centromere identity. Here, we review the progress and compendium of research on plant centromere in the light of recent data.     

Knockdown of CENH3 in Arabidopsis reduces mitotic divisions and causes sterility by disturbed meiotic chromosome segregation

The histone H3 variant (CENH3) of centromeric nucleosomes is essential for kinetochore assembly and thus for chromosome segregation in eukaryotes. The mechanism(s) that determine centromere identity, assembly and maintenance of kinetochores are still poorly understood. Although the role of CENH3 during mitosis has been studied in several organisms, little is known about its meiotic function. We show that RNAi-mediated CENH3 knockdown in Arabidopsis thaliana caused dwarfism as the result of a reduced number of mitotic divisions. The remaining mitotic divisions appeared to be error-free. CENH3 RNAi transformants had reduced fertility because of frequently disturbed meiotic chromosome segregation. N-terminally truncated EYFP-CENH3(C) is deposited to and functional within Arabidopsis centromeres of mitotic chromosomes, but cannot be loaded onto centromeres of meiotic nuclei. Thus the N-terminal part is apparently required for CENH3 loading during meiosis. EYFP-CENH3(C) expression reduces the amount of endogenous CENH3, thus mimicking the effect of RNAi. The consequences of reduced endogenous CENH3 and lack of meiotic incorporation of EYFP-CENH3(C) are reduced fertility caused by insufficient CENH3 loading to the centromeres of meiotic chromosomes, subsequent lagging of chromosomes and formation of micronuclei.     

Critical histone post-translational modifications for centromere function and propagation

The centromere is a critical genomic region that enables faithful chromosome segregation during mitosis, and must be distinguishable from other genomic regions to facilitate establishment of the kinetochore. The centromere-specific histone H3-variant CENP-A forms a special nucleosome that functions as a marker for centromere specification. In addition to the CENP-A nucleosomes, there are additional H3 nucleosomes that have been identified in centromeres, both of which are predicted to exhibit specific features. It is likely that the composite organization of CENP-A and H3 nucleosomes contributes to the formation of centromere-specific chromatin, termed ‘centrochromatin’. Recent studies suggest that centrochromatin has specific histone modifications that mediate centromere specification and kinetochore assembly. We use chicken non-repetitive centromeres as a model of centromeric activities to characterize functional features of centrochromatin. This review discusses our recent progress, and that of various other research groups, in elucidating the functional roles of histone modifications in centrochromatin.     

hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability

DNA2 is a nuclease/helicase that is involved in Okazaki fragment maturation, replication fork processing, and end resection of DNA double‐strand breaks. Similar such helicase activity for resolving secondary structures and structure‐specific nuclease activity are needed during DNA replication to process the chromosome‐specific higher order repeat units present in the centromeres of human chromosomes. Here, we show that DNA2 binds preferentially to centromeric DNA. The nuclease and helicase activities of DNA2 are both essential for resolution of DNA structural obstacles to facilitate DNA replication fork movement. Loss of DNA2‐mediated clean‐up mechanisms impairs centromeric DNA replication and CENP‐A deposition, leading to activation of the ATR DNA damage checkpoints at centromeric DNA regions and late‐S/G2 cell cycle arrest. Cells that escape arrest show impaired metaphase plate formation and abnormal chromosomal segregation. Furthermore, the DNA2 inhibitor C5 mimics DNA2 knockout and synergistically kills cancer cells when combined with an ATR inhibitor. These findings provide mechanistic insights into how DNA2 supports replication of centromeric DNA and give further insights into new therapeutic strategies.     

TeCK database: a comprehensive collection of telomeric and centromeric sequences with their associated proteins

Telomeres and centromere are two essential features of all eukaryotic chromosomes. They provide function that is necessary for the stability of chromosomes. We developed a comprehensive database named TeCK, which covers a gamut of sequence and other related information about telomeric patterns, telomere repeat sequences, centromere sequences and centromeric patterns present in chromosomes. It also contains information about telomerase ribo-nucleoprotein complexes, centromere binding protein and centromere DNA-binding protein complexes. The database also includes a collection of all kinetochore-associated proteins including inner, outer and central kinetochore proteins. The database can be searched using a user-friendly web interface. AVAILABILITY: http://www.bioinfosastra.com/services/teck/index.html.     

A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors

The Ndc80 complex is the key microtubule‐binding element of the kinetochore. In contrast to the well‐characterized interaction of Ndc80‐Nuf2 heads with microtubules, little is known about how the Spc24‐25 heterodimer connects to centromeric chromatin. Here, we present molecular details of Spc24‐25 in complex with the histone‐fold protein Cnn1/CENP‐T illustrating how this connection ultimately links microtubules to chromosomes. The conserved Ndc80 receptor motif of Cnn1 is bound as an α helix in a hydrophobic cleft at the interface between Spc24 and Spc25. Point mutations that disrupt the Ndc80–Cnn1 interaction also abrogate binding to the Mtw1 complex and are lethal in yeast. We identify a Cnn1‐related motif in the Dsn1 subunit of the Mtw1 complex, necessary for Ndc80 binding and essential for yeast growth. Replacing this region with the Cnn1 peptide restores viability demonstrating functionality of the Ndc80‐binding module in different molecular contexts. Finally, phosphorylation of the Cnn1 N‐terminus coordinates the binding of the two competing Ndc80 interaction partners. Together, our data provide structural insights into the modular binding mechanism of the Ndc80 complex to its centromere recruiters.