CENP-I directly targets centromeric DNA to support CENP-A deposition and centromere maintenance.
CENP-I directly targets centromeric DNA to support CENP-A deposition and centromere maintenance.
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CENP-I直接靶向Centromeric DNA，以支持CENP-A沉积和丝粒维持。
DOI：
10.1073/pnas.2219170120
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发表时间：
2023-03-14
影响因子：
11.1
通讯作者：
He, Xiaojing
中科院分区：
文献类型：
--
作者：
Hu, Liqiao;Zhao, Congcong;Liu, Mingjie;Liu, Shuaiyu;Ye, Jingjing;Wang, Kehui;Shi, Jinyun;Tian, Wei;He, Xiaojing
着丝点是一种多亚基蛋白质复合物，作为微管和染色体的平台，以确保细胞分裂过程中遗传物质的分离。组蛋白H3变体CENP-A在着丝粒处启动着丝点的组装。在这里，我们确定了亚基CENP-I和着丝粒DNA之间的物理相互作用。CENP-I通过其N端HEAT重复序列直接靶向着丝粒DNA中富含at的元素，并有助于CENP-I着丝粒的定位。这种相互作用是重新沉积CENP-A以维持着丝粒同一性所必需的。这些结果提供了着丝粒和着丝粒之间的直接联系，并为动态着丝粒组装提供了新的见解。组蛋白H3变体CENP-A的富集是着丝粒的表观遗传标记，并启动着丝粒的组装。着丝点是一个多亚基复合体，确保微管着丝粒的准确附着和姐妹染色单体在有丝分裂过程中的忠实分离。作为着丝点的亚基，CENP-I在着丝点的定位也依赖于CENP-A。然而，CENP-I是否以及如何调节CENP-A沉积和着丝粒身份尚不清楚。在这里，我们发现CENP-I直接与着丝粒DNA相互作用，并通过n端HEAT重复序列末端的保守带电残基形成的连续DNA结合表面优先识别富含at的DNA元素。DNA结合缺陷突变体保留了与CENP-H/K和CENP-M的相互作用，但显著降低了CENP-I的着丝粒定位和有丝分裂时的染色体排列。此外，新合成的CENP-A的着丝粒装载需要与CENP-I的DNA结合。通过结合核小体DNA而不是组蛋白来稳定CENP-A核小体。这些发现揭示了CENP-I促进和稳定CENP-A沉积的分子机制，对理解细胞周期中着丝粒和着丝点的动态相互作用具有重要意义。
The kinetochore is a multi-subunit protein complex that served as a platform for microtubules and chromosomes to ensure genetic material separation during cell division. Histone H3 variant CENP-A initiates the assembly of the kinetochore at centromere. Here, we identify a physical interaction between the subunit CENP-I and centromeric DNA. CENP-I directly targets AT-rich element of centromeric DNA via its N terminal HEAT repeats and contributes to CENP-I centromeric localization. This interaction is required for de novo CENP-A deposition to maintain centromere identity. These results offer a direct link between kinetochore and centromere and provide new insight into the dynamic kinetochore assembly. The enrichment of histone H3 variant CENP-A is the epigenetic mark of centromere and initiates the assembly of the kinetochore at centromere. The kinetochore is a multi-subunit complex that ensures accurate attachment of microtubule centromere and faithful segregation of sister chromatids during mitosis. As a subunit of kinetochore, CENP-I localization at centromere also depends on CENP-A. However, whether and how CENP-I regulates CENP-A deposition and centromere identity remains unclear. Here, we identified that CENP-I directly interacts with the centromeric DNA and preferentially recognizes AT-rich elements of DNA via a consecutive DNA-binding surface formed by conserved charged residues at the end of N-terminal HEAT repeats. The DNA binding–deficient mutants of CENP-I retained the interaction with CENP-H/K and CENP-M, but significantly diminished the centromeric localization of CENP-I and chromosome alignment in mitosis. Moreover, the DNA binding of CENP-I is required for the centromeric loading of newly synthesized CENP-A. CENP-I stabilizes CENP-A nucleosomes upon binding to nucleosomal DNA instead of histones. These findings unveiled the molecular mechanism of how CENP-I promotes and stabilizes CENP-A deposition and would be insightful for understanding the dynamic interplay of centromere and kinetochore during cell cycle.
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影响因子：
7.7
作者：
Drinnenberg IA;deYoung D;Henikoff S;Malik HS
通讯作者：
Malik HS
DOI：
10.1126/science.1259308
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Falk SJ;Guo LY;Sekulic N;Smoak EM;Mani T;Logsdon GA;Gupta K;Jansen LE;Van Duyne GD;Vinogradov SA;Lampson MA;Black BE
通讯作者：
Black BE
DOI：
10.1083/jcb.201001013
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carroll CW;Milks KJ;Straight AF
通讯作者：
Straight AF
影响因子：
21.3
作者：
Carroll, Christopher W.;Silva, Mariana C. C.;Godek, Kristina M.;Jansen, Lars E. T.;Straight, Aaron F.
通讯作者：
Straight, Aaron F.
影响因子：
3.5
作者：
Aldrup-Macdonald ME;Sullivan BA
通讯作者：
Sullivan BA