Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
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DOI：
10.1371/journal.pgen.0020110
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发表时间：
2006-07
期刊：
影响因子：
4.5
通讯作者：
Karpen GH
中科院分区：
文献类型：
--
作者：
Blower MD;Daigle T;Kaufman T;Karpen GH
着丝粒/动粒复合体通过确保有丝分裂和减数分裂过程中的染色体运动，在细胞和生物体的生存能力中起着至关重要的作用。动粒还介导纺锤体附着检查点（SAC），该检查点会延迟后期启动，直到所有染色体的动粒都实现与有丝分裂纺锤体的双极附着。CENP - A蛋白是着丝粒特异性的染色质成分，为动粒形成提供结构和功能基础。在此我们表明，果蝇胚胎中CENP - A（CID）基因纯合缺失突变的细胞表现出早期有丝分裂延迟。这种有丝分裂延迟不会因DNA损伤检查点失活而被抑制，并且不太可能是DNA损伤的结果。令人惊讶的是，SAC成分BUBR1的突变部分抑制了这种有丝分裂延迟。此外，尽管许多动粒蛋白（包括SAC成分）无法定位到动粒，但cid突变体对纺锤体破坏仍保留完整的SAC反应。我们提出，在没有持续的动粒定位的情况下，SAC成分能够监测纺锤体组装并抑制细胞周期进程。
遗传性状从一个细胞或生物体世代到下一世代的正常遗传依赖于准确的染色体复制和分离。有缺陷的染色体分离与出生缺陷和癌症有关。着丝粒是染色体上的一个单一位置，负责组装动粒，动粒介导染色体与微管纺锤体的附着以及所有染色体运动。此外，纺锤体组装检查点（SAC）在染色体 - 纺锤体附着有缺陷时通过延迟进入后期来确保正常遗传。先前的研究表明，SAC功能需要关键成分在动粒上定位。这项研究表明，消除一种着丝粒特异性组蛋白（CID）会导致早期有丝分裂延迟。尽管这种延迟发生在比已确定的SAC功能时间（在中期 - 后期转换时）更早，但它依赖于一种必需的SAC蛋白（BUBR1）的存在。此外，CID介导的早期有丝分裂延迟发生在没有动粒形成或关键SAC蛋白定位的情况下。这些结果表明，在有丝分裂早期，并且在没有动粒形成和SAC成分定位的情况下，动粒 - 微管附着的准确性也受到监测。
The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID) display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization. Normal inheritance of genetic traits from one cell or organismal generation to the next depends on accurate chromosome replication and segregation. Defective chromosome segregation is associated with birth defects and cancer. The centromere is a single site on the chromosome that is responsible for assembling the kinetochore, which mediates chromosome attachment to the microtubule spindle and all chromosome movements. In addition, the spindle assembly checkpoint (SAC) ensures normal inheritance by delaying entry into anaphase when chromosome–spindle attachments are defective. Previous studies suggested that SAC function required kinetochore localization of key components. This study shows that elimination of a centromere-specific histone (CID) results in an early mitotic delay. Although this delay occurs earlier than the established time of SAC function (at the metaphase–anaphase transition), it depends on the presence of an essential SAC protein (BUBR1). Furthermore, the CID-mediated early mitotic delay occurs in the absence of kinetochore formation or localization of key SAC proteins. These results suggest that the fidelity of kinetochore–microtubule attachment is also monitored early in mitosis, and in the absence of kinetochore formation and localization of SAC components.
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影响因子：
10.5
作者：
Heeger, S;Leismann, O;Lehner, CF
通讯作者：
Lehner, CF
影响因子：
11.4
作者：
Fukagawa, T;Mikami, Y;Ikemura, T
通讯作者：
Ikemura, T
DOI：
10.1083/jcb.200210005
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goshima G;Kiyomitsu T;Yoda K;Yanagida M
通讯作者：
Yanagida M
DOI：
10.1083/jcb.200211048
发表时间：
2003-02-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Babu JR;Jeganathan KB;Baker DJ;Wu X;Kang-Decker N;van Deursen JM
通讯作者：
van Deursen JM
DOI：
10.1073/pnas.97.3.1148
发表时间：
2000-02-01
影响因子：
11.1
作者：
Howman, EV;Fowler, KJ;Choo, KHA
通讯作者：
Choo, KHA