Bridgin connects the outer kinetochore to centromeric chromatin.

Bridgin connects the outer kinetochore to centromeric chromatin.
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DOI:
10.1038/s41467-020-20161-9
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发表时间:
2021-01-08
影响因子:
16.6
通讯作者:
Sanyal K
Sanyal K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sridhar S;Hori T;Nakagawa R;Fukagawa T;Sanyal K

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微管结合外动粒通过CENP-CMif 2、CENP-TCnn 1和CENP-UAme 1连接子途径与着丝粒染色质偶联,这些连接子途径源自内动粒的组成性着丝粒相关网络(CCAN)。在这里,我们证明了大多数CCAN组件,包括某些动粒连接器的真菌门的担子菌门的进化过程中经常性的损失。通过在模式担子菌和人类病原体新型隐球菌中的动粒相互作用组分析,将包含叉头相关结构域的蛋白质“bridgin”与其他预测的动粒蛋白一起鉴定为动粒组分沿着。在体内和体外的功能分析表明,桥蛋白连接外着丝粒染色质,以确保准确的染色体分离的能力。与已建立的基于CCAN的接头不同,桥蛋白在外部动粒处被招募,从而确立其作为动粒蛋白的独特家族的作用。在非真菌谱系中存在桥接同源物表明存在一种古老的趋异策略,以桥接外动粒与着丝粒染色质。动粒是一种复杂的结构,有助于将染色体附着在纺锤体微管上,确保细胞分裂过程中染色体的准确分离。着丝粒被认为是进化上保守的,但哪些成分是保守的还不清楚。在这里,作者报告说,一些成员的真菌门的Basidomycota缺乏许多传统的动粒连接蛋白。相反,它们拥有一种人类Ki 67样蛋白,将动粒的外部连接到着丝粒DNA,这可能会弥补常规接头的丢失。
The microtubule-binding outer kinetochore is coupled to centromeric chromatin through CENP-CMif2, CENP-TCnn1, and CENP-UAme1 linker pathways originating from the constitutive centromere associated network (CCAN) of the inner kinetochore. Here, we demonstrate the recurrent loss of most CCAN components, including certain kinetochore linkers during the evolution of the fungal phylum of Basidiomycota. By kinetochore interactome analyses in a model basidiomycete and human pathogen Cryptococcus neoformans, a forkhead-associated domain containing protein “bridgin” was identified as a kinetochore component along with other predicted kinetochore proteins. In vivo and in vitro functional analyses of bridgin reveal its ability to connect the outer kinetochore with centromeric chromatin to ensure accurate chromosome segregation. Unlike established CCAN-based linkers, bridgin is recruited at the outer kinetochore establishing its role as a distinct family of kinetochore proteins. Presence of bridgin homologs in non-fungal lineages suggests an ancient divergent strategy exists to bridge the outer kinetochore with centromeric chromatin. The kinetochore is a multi-complex structure that helps attach chromosomes to spindle microtubules, ensuring accurate chromosome segregation during cell division. Kinetochores are thought to be evolutionarily conserved, but which components are conserved is unclear. Here, the authors report that some members of the fungal phylum of Basidomycota lack many conventional kinetochore linker proteins. Instead, they possess a human Ki67-like protein that bridges the outer part of the kinetochore to centromere DNA, which may compensate for the loss of a conventional linker.
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