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Histone H2B mutations in inner region affect ubiquitination, centromere function, silencing and chromosome segregation
Author(s) -
Maruyama Takeshi,
Nakamura Takahiro,
Hayashi Takeshi,
Yanagida Mitsuhiro
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601110
Subject(s) - biology , centromere , histone h2b , genetics , gene silencing , histone , chromosome , kinetochore , microbiology and biotechnology , dna , gene
The reiterated nature of histone genes has hampered genetic approach to dissect the role of histones in chromatin dynamics. We here report isolation of three temperature‐sensitive ( ts ) Schizosaccharomyces pombe strains, containing amino‐acid substitutions in the sole histone H2B gene ( htb1 + ). The mutation sites reside in the highly conserved, non‐helical residues of H2B, which are implicated in DNA–protein or protein–protein interactions in the nucleosome. In the allele of htb1‐72 , the substitution (G52D) occurs at the DNA binding loop L1, causing disruption of the gene silencing in heterochromatic regions and lagging chromosomes in anaphase. In another allele htb1‐223 (P102L) locating in the junction between α3 and αC, the mutant residue is in contact with H2A and other histones, leading to structural aberrations in the central centromere chromatin and unequal chromosome segregation in anaphase. The third allele htb1‐442 (E34K) near α1 displayed little defect. Evidence is provided that monoubiquitinated H2B is greatly unstable in P102L mutant, possibly owing to proteasome‐independent destruction or enhanced deubiquitination. Histone H2B thus plays an important role in centromere/kinetochore formation.