Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation.
Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation.
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DOI：
10.1038/s41467-021-27131-9
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发表时间：
2021-12-01
影响因子：
16.6
通讯作者：
Draviam VM
中科院分区：
文献类型：
--
作者：
Song X;Conti D;Shrestha RL;Braun D;Draviam VM
染色体-微管附着缺陷可导致染色体不稳定性（CIN），通常与不育和侵袭性癌症有关。染色体-微管的附着是由一个大的大分子结构，动粒介导的。每个染色体的姐妹动粒被微管从相对的纺锤极拉出来，这种状态称为双取向，可以防止染色体的错误分离。缺乏相反拉力的运动舞蹈微管附件被Aurora-B/Ipl 1分离。目前还不清楚为什么在双定向之前的单定向附着体在缺乏反向拉力的情况下会幸免于难。使用RNAi筛选，我们发现了Astrin-SKAP复合物在保护单取向附件中的独特作用。我们提供了微管末端相关蛋白质中的结构域的证据，该结构域感测末端着丝粒微管附件的特异性变化，并组装外着丝粒新月以稳定附件。我们发现，Astrin-PP 1和细胞周期蛋白-B-CDK 1途径相互抵消，以保持单向连接。因此，CIN预防途径不仅要调查附件缺陷，而且要主动识别和稳定独立于双向的成熟附件。由于染色体-微管附着的问题，经常发生染色体不稳定性。在这里，作者表明，Astrin-PP 1和Cyclin-B-CDK 1途径相互抵消，以保护染色体微管附着独立于双向。
Defects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome missegregation. Kinetochore-microtubule attachments that lack the opposing-pull are detached by Aurora-B/Ipl1. It is unclear how mono-oriented attachments that precede biorientation are spared despite the lack of opposing-pull. Using an RNAi-screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide evidence of domains in the microtubule-end associated protein that sense changes specific to end-on kinetochore-microtubule attachments and assemble an outer-kinetochore crescent to stabilise attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to preserve mono-oriented attachments. Thus, CIN prevention pathways are not only surveying attachment defects but also actively recognising and stabilising mature attachments independent of biorientation. Chromosome instability frequently occurs due to issues with chromosome-microtubule attachments. Here the authors show that the Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to protect chromosome-microtubule attachments independent of biorientation.
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影响因子：
21.3
作者：
Bakhoum, Samuel F.;Thompson, Sarah L.;Manning, Amity L.;Compton, Duane A.
通讯作者：
Compton, Duane A.
DOI：
10.4161/cc.25671
发表时间：
2013-08-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Corrigan AM;Shrestha RL;Zulkipli I;Hiroi N;Liu Y;Tamura N;Yang B;Patel J;Funahashi A;Donald A;Draviam VM
通讯作者：
Draviam VM
影响因子：
44.1
作者：
Chen, Qiang;Zhang, Xiaoyan;Zhang, Chuamnao
通讯作者：
Zhang, Chuamnao
影响因子：
11.4
作者：
Draviam, V. M.;Shapiro, I.;Sorger, P. K.
通讯作者：
Sorger, P. K.
影响因子：
8.8
作者：
Drpic, Danica;Pereira, Antonio J.;Maiato, Helder
通讯作者：
Maiato, Helder