Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation.
Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation.
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DOI：
10.1038/ncomms5951
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发表时间：
2014-09-19
影响因子：
16.6
通讯作者：
Davis, Trisha N.
中科院分区：
文献类型：
--
作者：
Umbreit, Neil T.;Miller, Matthew P.;Tien, Jerry F.;Ortola, Jerome Cattin;Gui, Long;Lee, Kelly K.;Biggins, Sue;Asbury, Charles L.;Davis, Trisha N.
着丝粒在着丝粒 DNA 上组装，并呈现直接附着在微管动态末端的蛋白质阵列。着丝粒蛋白通过寡聚化在微管界面上进行协调，但寡聚化如何促进着丝粒功能仍不清楚。在这里，结合生物物理测定和活细胞成像，我们发现 Dam1 着丝粒复合物的寡聚是其形成微管附着物的能力所必需的，这些微管附着物在体外和体内都能抵抗张力。保留野生型微管结合活性的寡聚化缺陷的 Dam1 复合物主要在体外激光陷阱施加的机械负载下耦合解体微管末端方面存在缺陷。在细胞中，寡聚化缺陷的 Dam1 复合物无法支持姐妹染色单体的稳定双极排列，表明着丝粒-微管附着在张力下失败。我们认为寡聚化是着丝粒成分的一个重要且保守的特征，是有丝分裂期间准确染色体分离所必需的。
Kinetochores assemble on centromeric DNA and present arrays of proteins that attach directly to the dynamic ends of microtubules. Kinetochore proteins coordinate at the microtubule interface through oligomerization, but how oligomerization contributes to kinetochore function has remained unclear. Here, using a combination of biophysical assays and live-cell imaging, we find that oligomerization of the Dam1 kinetochore complex is required for its ability to form microtubule attachments that are robust against tension in vitro and in vivo. An oligomerization-deficient Dam1 complex that retains wild-type microtubule binding activity is primarily defective in coupling to disassembling microtubule ends under mechanical loads applied by a laser trap in vitro. In cells, the oligomerization-deficient Dam1 complex is unable to support stable bipolar alignment of sister chromatids, indicating failure of kinetochore-microtubule attachments under tension. We propose that oligomerization is an essential and conserved feature of kinetochore components that is required for accurate chromosome segregation during mitosis.
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影响因子：
16.8
作者：
Miranda, JJL;De Wulf, P;Harrison, SC
通讯作者：
Harrison, SC
DOI：
10.1083/jcb.200912021
发表时间：
2010-05-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lampert F;Hornung P;Westermann S
通讯作者：
Westermann S
影响因子：
21.3
作者：
Gestaut, Daniel R.;Graczyk, Beth;Davis, Trisha N.
通讯作者：
Davis, Trisha N.
影响因子：
21.3
作者：
Franck, Andrew D.;Powers, Andrew F.;Asbury, Charles L.
通讯作者：
Asbury, Charles L.
DOI：
10.1073/pnas.0709524104
发表时间：
2007-11-27
影响因子：
11.1
作者：
Efremov, Artem;Grishchuk, Ekaterina L.;Ataullakhanov, Fazly I.
通讯作者：
Ataullakhanov, Fazly I.