Centromere targeting of Mis18 requires the interaction with DNA and H2A–H2B in fission yeast

Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on the centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the cent...

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Veröffentlicht in:Cellular and molecular life sciences : CMLS 2021-01, Vol.78 (1), p.373-384
Hauptverfasser: Zhang, Min, Zheng, Fan, Xiong, Yujie, Shao, Chen, Wang, Chengliang, Wu, Minhao, Niu, Xiaojia, Dong, Fenfen, Zhang, Xuan, Fu, Chuanhai, Zang, Jianye
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container_title Cellular and molecular life sciences : CMLS
container_volume 78
creator Zhang, Min
Zheng, Fan
Xiong, Yujie
Shao, Chen
Wang, Chengliang
Wu, Minhao
Niu, Xiaojia
Dong, Fenfen
Zhang, Xuan
Fu, Chuanhai
Zang, Jianye
description Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on the centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the centromere loading of the newly-synthesized CENP-A. However, it remains unclear how Mis18 complex ( sp Mis18, sp Mis16 and sp Mis19) is located to the centromere to license the recruitment of Cnp1 CENP-A in Schizosaccharomyces pombe . We found that sp Mis18 directly binds to nucleosomal DNA through its extreme C-terminus and interacts with H2A–H2B dimer via the acidic region on the surface of its Yippee-like domain. Live-cell imaging confirmed that mutation of the acidic region and deletion of the extreme C-terminus significantly impairs the localization of sp Mis18 and Cnp1 to the centromere and delays chromosome segregation during mitosis. Our findings illustrate that the interaction of sp Mis18 with histone H2A–H2B and DNA plays important roles in the recruitment of sp Mis18 and Cnp1 to the centromere in fission yeast.
doi_str_mv 10.1007/s00018-020-03502-1
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CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the centromere loading of the newly-synthesized CENP-A. However, it remains unclear how Mis18 complex ( sp Mis18, sp Mis16 and sp Mis19) is located to the centromere to license the recruitment of Cnp1 CENP-A in Schizosaccharomyces pombe . We found that sp Mis18 directly binds to nucleosomal DNA through its extreme C-terminus and interacts with H2A–H2B dimer via the acidic region on the surface of its Yippee-like domain. Live-cell imaging confirmed that mutation of the acidic region and deletion of the extreme C-terminus significantly impairs the localization of sp Mis18 and Cnp1 to the centromere and delays chromosome segregation during mitosis. 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Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on the centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the centromere loading of the newly-synthesized CENP-A. However, it remains unclear how Mis18 complex ( sp Mis18, sp Mis16 and sp Mis19) is located to the centromere to license the recruitment of Cnp1 CENP-A in Schizosaccharomyces pombe . We found that sp Mis18 directly binds to nucleosomal DNA through its extreme C-terminus and interacts with H2A–H2B dimer via the acidic region on the surface of its Yippee-like domain. Live-cell imaging confirmed that mutation of the acidic region and deletion of the extreme C-terminus significantly impairs the localization of sp Mis18 and Cnp1 to the centromere and delays chromosome segregation during mitosis. Our findings illustrate that the interaction of sp Mis18 with histone H2A–H2B and DNA plays important roles in the recruitment of sp Mis18 and Cnp1 to the centromere in fission yeast.</description><subject>Assembly</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>C-Terminus</subject><subject>Carrier Proteins - chemistry</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Biology</subject><subject>Centromere - metabolism</subject><subject>Centromere protein A</subject><subject>Chromatin</subject><subject>Chromosomal Proteins, Non-Histone - genetics</subject><subject>Chromosomal Proteins, Non-Histone - metabolism</subject><subject>Chromosome Segregation</subject><subject>Chromosomes</subject><subject>Crystallography, X-Ray</subject><subject>Deoxyribonucleic 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Live-cell imaging confirmed that mutation of the acidic region and deletion of the extreme C-terminus significantly impairs the localization of sp Mis18 and Cnp1 to the centromere and delays chromosome segregation during mitosis. Our findings illustrate that the interaction of sp Mis18 with histone H2A–H2B and DNA plays important roles in the recruitment of sp Mis18 and Cnp1 to the centromere in fission yeast.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>32318758</pmid><doi>10.1007/s00018-020-03502-1</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Assembly
Biochemistry
Biomedical and Life Sciences
Biomedicine
C-Terminus
Carrier Proteins - chemistry
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Biology
Centromere - metabolism
Centromere protein A
Chromatin
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Chromosome Segregation
Chromosomes
Crystallography, X-Ray
Deoxyribonucleic acid
Dimerization
Dimers
DNA
DNA - chemistry
DNA - metabolism
Fission
Gene deletion
Histone H2A
Histone H3
Histones
Histones - genetics
Histones - metabolism
Life Sciences
Localization
Microscopy, Fluorescence
Mitosis
Molecular Dynamics Simulation
Multiprotein Complexes - chemistry
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Mutagenesis
Mutation
Original
Original Article
Protein Binding
Protein Domains
Protein Structure, Tertiary
Recruitment
Schizosaccharomyces - genetics
Schizosaccharomyces - metabolism
Schizosaccharomyces pombe Proteins - chemistry
Schizosaccharomyces pombe Proteins - genetics
Schizosaccharomyces pombe Proteins - metabolism
Time-Lapse Imaging
Yeast
Yeasts
title Centromere targeting of Mis18 requires the interaction with DNA and H2A–H2B in fission yeast
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