Human chromokinesin KIF4A functions in chromosome condensation and segregation.
Human chromokinesin KIF4A functions in chromosome condensation and segregation.
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DOI：
10.1083/jcb.200401142
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发表时间：
2004-08-30
期刊：
影响因子：
--
通讯作者：
Misteli T
中科院分区：
文献类型：
--
作者：
Mazumdar M;Sundareshan S;Misteli T
染色体在中期的精确配对和随后的浓缩染色体的分离是一个复杂的过程，涉及复杂的、仅部分描述的分子机制。尽管几个纺锤体相关的分子马达已经被证明是有丝分裂功能所必需的，但只有少数与染色体臂相关的马达被描述。在这里，我们证明了人的染色质在人的HKIF4A(HKIF4A)是一个重要的染色体相关的分子马达，参与了忠实的染色体分离。HKIF4A在间期定位于核质，在有丝分裂时定位于浓缩的染色体臂上。从后期开始在中部聚集，在胞质分裂时定位于细胞动态环。RNA干扰介导的HKIF4A缺失导致人类细胞前中期组织缺陷、中期染色体错位、纺锤体缺陷和染色体错误分离。HKIF4A与凝聚素I和II复合体相互作用，HKIF4A缺失会导致染色体超凝聚，这表明HKIF4A是维持正常染色体构型所必需的。我们的结果提供了功能证据，证明人类KIF4A是染色体凝聚和分离机制中的一个新组件，在有丝分裂的多个步骤中发挥作用。
Accurate chromosome alignment at metaphase and subsequent segregation of condensed chromosomes is a complex process involving elaborate and only partially characterized molecular machinery. Although several spindle associated molecular motors have been shown to be essential for mitotic function, only a few chromosome arm–associated motors have been described. Here, we show that human chromokinesin human HKIF4A (HKIF4A) is an essential chromosome-associated molecular motor involved in faithful chromosome segregation. HKIF4A localizes in the nucleoplasm during interphase and on condensed chromosome arms during mitosis. It accumulates in the mid-zone from late anaphase and localizes to the cytokinetic ring during cytokinesis. RNA interference–mediated depletion of HKIF4A in human cells results in defective prometaphase organization, chromosome mis-alignment at metaphase, spindle defects, and chromosome mis-segregation. HKIF4A interacts with the condensin I and II complexes and HKIF4A depletion results in chromosome hypercondensation, suggesting that HKIF4A is required for maintaining normal chromosome architecture. Our results provide functional evidence that human KIF4A is a novel component of the chromosome condensation and segregation machinery functioning in multiple steps of mitotic division.
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