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Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N
被引:88
作者:

Chittori, Sagar
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NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA

Hong, Jingjun
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NCI, Lab Biochem & Mol Biol, CCR, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA

Saunders, Hayden
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NCI, Lab Biochem & Mol Biol, CCR, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA

Feng, Hanqiao
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NCI, Lab Biochem & Mol Biol, CCR, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA

Ghirlando, Rodolfo
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NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA

Kelly, Alexander E.
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NCI, Lab Biochem & Mol Biol, CCR, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA

Bai, Yawen
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NCI, Lab Biochem & Mol Biol, CCR, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA

Subramaniam, Sriram
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NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA
机构:
[1] NCI, Lab Cell Biol, CCR, NIH, Bethesda, MD 20892 USA
[2] NCI, Lab Biochem & Mol Biol, CCR, NIH, Bethesda, MD 20892 USA
[3] NIDDK, Lab Mol Biol, NIH, Bethesda, MD 20892 USA
来源:
关键词:
A NUCLEOSOMES;
CHROMATIN;
HISTONE;
ORGANIZATION;
ARCHITECTURE;
HETERODIMER;
COMPLEX;
D O I:
10.1126/science.aar2781
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo-electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.
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页码:339 / +
页数:5
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NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA

Bai, Yawen
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机构:
NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA