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CENP-A is dispensable for mitotic centromere function after initial centromere/kinetochore assembly

机译:CENP-A可用于初始着丝粒/动粒组装后的有丝分裂着丝粒功能

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摘要

Human centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation. Without the continuing presence of CENP-A, CENP-B binding to alphoid DNA sequences becomes essential to preserve anchoring of CENP-C and the kinetochore to each centromere. Thus, there is a reciprocal interdependency of CENP-A chromatin and the underlying repetitive centromere DNA sequences bound by CENP-B in the maintenance of human chromosome segregation.
机译:人类着丝粒是由染色质定义的,该染色质包含装配在重复的类脂DNA序列上的组蛋白H3变体CENP-A。通过诱导内源性CENP-A的快速,完全降解,我们现在证明,一旦在G1 / S中完成着丝粒装配的第一步,就不再需要持续的CENP-A结合来保持动粒体附着在着丝粒上或着丝粒的功能。下一个有丝分裂。发现在线粒体组装之前,CENP-A的降解会阻止CENP-C和CENP-N的沉积,但不会阻止CENP-T的沉积,从而产生有缺陷的动臂和染色体分离失败。没有CENP-A的持续存在,CENP-B与脂质DNA序列的结合就必须保持CENP-C和动粒体对每个着丝粒的锚定。因此,在维持人类染色体分离中,CENP-A染色质与CENP-B结合的潜在重复着丝粒DNA序列存在相互依存关系。

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