CENPA

更新于：2025-05-07

基本信息

别名

CenH3、CENP-A、CENPA

+ [3]

简介

Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:11756469, PubMed:14667408, PubMed:15282608, PubMed:15475964, PubMed:15702419, PubMed:17651496, PubMed:19114591, PubMed:20739937, PubMed:27499292, PubMed:7962047, PubMed:9024683). Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner kinetochore (PubMed:18072184). The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3 (PubMed:26878239, PubMed:27499292). May serve as an epigenetic mark that propagates centromere identity through replication and cell division (PubMed:15282608, PubMed:15475964, PubMed:20739937, PubMed:21478274, PubMed:26878239). Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis (PubMed:11756469, PubMed:14667408, PubMed:18072184, PubMed:23818633, PubMed:25556658, PubMed:27499292).

关联

100 项与 CENPA 相关的临床结果

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100 项与 CENPA 相关的转化医学

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0 项与 CENPA 相关的专利（医药）

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1,538

项与 CENPA 相关的文献（医药）

2025-12-01·Chromosoma

Towards identification of a holocentromere marker in the lepidopteran model Spodoptera frugiperda

Article

作者: Legeai, Fabrice ; d'Alençon, Emmanuelle ; Gamble, Sally ; Gimenez, Sylvie ; Eychenne, Magali

Some insects have holocentric chromosomes, with multiple kinetochores rather than a single centromere. They also lack the CENP-A and CENP-C proteins, suggesting a kinetochore assembly process different from that of monocentric chromosomes. The homolog of CENP-T was recently shown to bind silent chromatin and to play a key role in kinetochore assembly in Bombyx mori, but its role in other insects with holocentric chromosomes is unknown. We identified kinetochore genes and analyzed their expression in Spodoptera frugiperda. We silenced the kinetochore genes cenp-L, cenp-S, cenp-X and ndc80 and searched for chromosome segregation defects in Sf9 cells. All kinetochore genes except cenp-S were more strongly expressed in gonadal than in somatic tissues. Immunofluorescence microscopy and RT-qPCR demonstrated the effective silencing of the target genes by transfection with dsRNA. In Sf9 cells depleted of CENP-L and NDC80, immunofluorescence microscopy revealed increases in mitotic index and in the proportion of cells with unaligned chromosomes or multipolar spindles. The depletion of CENP-S and CENP-X had no effect on mitotic index and no division defects were observed. This suggests that CENP-L and NDC80 play key roles in chromosome segregation, whereas the functions of CENP-S and CENP-X remain unknown. We have begun to characterize the kinetochore proteins (CENP-L, CENP-S, CENP-X, NDC80), a prerequisite for holocentromere identification in S. frugiperda. This study also provides the first information about the role, in Lepidoptera, of CENP-L, a protein essential to the structure of the constitutive centromere-associated network in species with monocentric chromosomes.

2025-07-01·Biotechnology Advances

Advances in gene editing-led route for hybrid breeding in crops

Review

作者: Farooq, Muhammad Awais ; Ehsan, Aiman ; Hensel, Goetz ; Buzdar, Muhammad Ismail ; Zia, Asma ; Awan, Muhammad Jawad Akbar ; Mansoor, Shahid ; Amin, Imran ; Waqas, Muhammad Abu Bakar

With the global demand for sustainable agriculture on the rise, RNA-guided nuclease technology offers transformative applications in crop breeding. Traditional hybrid breeding methods, like three-line and two-line systems, are often labor-intensive, transgenic, and economically burdensome. While chemical mutagens facilitate these systems, they not only generate weak alleles but also produce strong alleles that induce permanent sterility through random mutagenesis. In contrast, RNA-guided nuclease system, such as clustered regularly interspaced short palindromic repeats (CRISPR)- associated protein (Cas) system, facilitates more efficient hybrid production by inducing male sterility through targeted genome modifications in male sterility genes, such as MS8, MS10, MS26, and MS45 which allows precise manipulation of pollen development or pollen abortion in various crops. Moreover, this approach allows haploid induction for the rapid generation of recombinant and homozygous lines from hybrid parents by editing essential genes, like CENH3, MTL/NLD/PLA, and DMP, resulting in high-yield, transgene-free hybrids. Additionally, this system supports synthetic apomixis induction by employing the MiMe (Mitosis instead of Meiosis) strategy, coupled with parthenogenesis in hybrid plants, to create heterozygous lines and retain hybrid vigor in subsequent generations. RNA-guided nuclease-induced synthetic apomixis also enables genome stacking for autopolyploid progressive heterosis via clonal gamete production for trait maintenance to enhance crop adaptability without compromising yield. Additionally, CRISPR-Cas-mediated de novo domestication of wild relatives, along with recent advances to circumvent tissue culture- recalcitrance and -dependency through heterologous expression of morphogenic regulators, holds great promise for incorporating diversity-enriched germplasm into the breeding programs. These approaches aim to generate elite hybrids adapted to dynamic environments and address the anticipated challenges of food insecurity.

2025-05-05·Journal of Cell Biology

Interactions with multiple inner kinetochore proteins determine mitotic localization of FACT

Article

作者: Hoffmann, Ingrid ; Mulay, Bhagyashree ; Vogt, Doro ; Musacchio, Andrea ; Pesenti, Marion E. ; Schweighofer, Julia

The FAcilitates Chromatin Transcription (FACT) complex is a dimeric histone chaperone that operates on chromatin during transcription and replication. FACT also interacts with a specialized centromeric nucleosome containing the histone H3 variant centromere protein A (CENP-A) and with CENP-TW, two subunits of the constitutive centromere–associated network (CCAN), a 16-protein complex associated with CENP-A. The significance of these interactions remains elusive. Here, we show that FACT has multiple additional binding sites on CCAN. The interaction with CCAN is strongly stimulated by casein kinase II phosphorylation of FACT. Mitotic localization of FACT to kinetochores is strictly dependent on specific CCAN subcomplexes. Conversely, CENP-TW requires FACT for stable localization. Unexpectedly, we also find that DNA readily displaces FACT from CCAN, supporting the speculation that FACT becomes recruited through a pool of CCAN that is not stably integrated into chromatin. Collectively, our results point to a potential role of FACT in chaperoning CCAN during transcription or in the stabilization of CCAN at the centromere during the cell cycle.

项与 CENPA 相关的新闻（医药）

2024-10-05

·奇点网

爱玩儿火的癌细胞，准备好了灭火器🧯

*仅供医学专业人士阅读参考在我看来，癌细胞最疯狂的行为当属染色体不稳定性增加。虽然增加染色体不稳定性有助于癌细胞的进展和耐药，但是过度不稳定必然会导致细胞死亡。因此，我每次看到相关研究论文时，心中都有一个疑问：不断在死亡边缘试探的癌细胞，究竟是如何免于一死的？或者，癌细胞究竟是如何避免染色体不稳定性失控的？近日，由北京大学生命科学学院刘君和清华大学生命科学学院杨雪瑞领衔的研究团队，在顶级期刊《细胞》上发表一项重磅研究成果[1]，解答了我心中的疑问。他们发现，与正常细胞相比，癌细胞的着丝粒RNA上m6A甲基化修饰水平升高，这会导致着丝粒蛋白A与着丝粒RNA结合更紧密，帮助着丝粒蛋白A定位于着丝粒，进而维持有丝分裂期间着丝粒的完整性和功能，保证染色体的正确分离和稳定性。值得注意的是，只要降低着丝粒RNA的m6A修饰水平，或阻断着丝粒蛋白A与着丝粒RNA的结合，都会导致着丝粒完整性受损和染色体分离异常，最终抑制癌细胞增殖和肿瘤生长。这也意味着，新的抗癌疗法有望诞生。北京大学康自红和清华大学李瑞萌是论文的共同第一作者。▲ 论文首页截图在细胞的有丝分裂过程中，着丝粒对于染色体的正确分离至关重要。如果着丝粒的完整性被破坏，就会导致错误分离的染色体迅速积累，产生非整倍体，这恰好就是癌细胞的一个特征。近年来，有研究发现，由着丝粒区域转录出的着丝粒RNA（cenRNA），似乎参与调控着丝粒稳态和细胞周期进程，但科学家对背后机制仍知之甚少。鉴于RNA的m6A修饰与多种疾病有关，且染色质相关RNA（caRNAs）上也存在m6A修饰，刘君/杨雪瑞团队想知道，m6A修饰是否与癌细胞染色体稳定性有关。于是，他们研究的第一步就是分析了五种癌细胞系（A375、HEC-1-A、HepG2、K562和MCF7）和两种正常细胞系（IMR90和HEK293T）中各种RNA的甲基化水平。从研究结果来看，与正常细胞相比，癌细胞中cenRNAs表现出更高的m6A修饰率（60%）和总体水平。▲ cenRNAs浮出水面鉴于m6A修饰由甲基化酶METTL3负责，研究人员就构建了METTL3被敲除的A375细胞系（人恶性黑色素瘤细胞），发现METTL3被敲除后，cenRNA的m6A修饰水平下降最为显著。这说明，cenRNA的m6A修饰确实是由METTL3完成的。在METTL3被敲除的A375细胞系中，研究人员还观察到染色体易位和着丝粒断裂的频率显著增加。类似地，用靶向去甲基化工具特异性擦除cenRNA上的m6A修饰，也会导致染色体变异。不难看出，cenRNA的m6A修饰确实参与维持着丝粒的稳定性。▲ cenRNA的m6A修饰参与维持着丝粒的稳定性接下来的问题是，cenRNA的m6A修饰是如何影响着丝粒稳定性的呢？刘君/杨雪瑞团队又开始筛选与m6A修饰的cenRNA相互作用的关键蛋白。通过对比METTL3敲除前后结合水平的变化，着丝粒蛋白A（CENPA）被挖出来了。他们还发现，在METTL3被敲除或m6A修饰被抹除之后，A375细胞着丝粒位点内的CENPA减少。此外，他们还证实，CENPA更倾向于跟m6A修饰的cenRNA结合；或者说，m6A修饰会增强CENPA与cenRNA的亲和力。其中，起到关键作用的是CENPA上的Leu61和Arg63。▲ CENPA与m6A修饰cenRNA结合的关键氨基酸残基随后，刘君/杨雪瑞团队评估了CENPA与m6A修饰cenRNA相互作用，对着丝粒完整性的影响。他们发现，无论是敲除癌细胞的METTL3，还是抹除癌细胞的m6A修饰，都会导致基因组不稳定事件全面增加，而且这些不稳定事件在着丝粒区域高度富集。在CENPA被敲除的癌细胞中，着丝粒损伤增加/细胞周期被扰乱，只有过表达野生型的CENPA才能逆转着丝粒损伤和细胞周期。以上结果说明，CENPA与m6A修饰cenRNA的优先结合，对维持着丝粒稳定性和正常细胞周期至关重要。▲ CENPA对细胞周期的影响进一步的研究表明，无论是降低癌细胞cenRNA的m6A修饰水平，还是敲除癌细胞的CENPA，都会导致染色体不稳定增加和DNA受损严重，以及癌细胞的生长和增殖受到抑制。此外，METTL3抑制剂还可以增加着丝粒活性干扰药物的效果。值得注意的是，cenRNA的m6A修饰对正常细胞影响较小，这也意味着靶向CENPA或m6A修饰cenRNA的抗癌思路有一定的可行性。▲ 机制示意图总的来说，刘君/杨雪瑞团队这项研究成果，揭示了癌细胞维持染色体稳定的潜在机制，让我们对着丝粒的形成、维持与调控有了新认知。更重要的是，这项研究成果还为癌症治疗提供了新靶点，也为新的靶向联合治疗提供了新思路。奇点糕近期推出了《2024ASCO年会深度盘点》课程，为大家系统盘点了2024ASCO年会上实体瘤领域的重磅进展，让您在100分钟内迅速深入把握前沿。长按识别下图中的二维码即可购买，购买后您可以在「奇点网小程序」收听，或下载奇点网「医学奇点」苹果客户端收听。如果遇到任何技术问题，大家可以戳我们下图中的客服小伙伴来解决~~参考文献：[1].Kang Z, Li R, Liu C, et al. m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells. Cell. Published online September 18, 2024. doi:10.1016/j.cell.2024.08.040本文作者丨BioTalker

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