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

• Published in: Cellular and molecular life sciences : CMLS Vol. 78; no. 1; pp. 373 - 384
• Main Authors: Zhang, Min, Zheng, Fan, Xiong, Yujie, Shao, Chen, Wang, Chengliang, Wu, Minhao, Niu, Xiaojia, Dong, Fenfen, Zhang, Xuan, Fu, Chuanhai, Zang, Jianye
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2021; Springer Nature B.V
• 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; Mis18; Histone H2A–H2B; Centromere; Cnp1; DNA
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-020-03502-1

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.