Altered dosage and mislocalization of histone H3 and Cse4p lead to chromosome loss in Saccharomyces cerevisiae
Altered dosage and mislocalization of histone H3 and Cse4p lead to chromosome loss in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.108.088518
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发表时间：
2008-05-01
期刊：
影响因子：
3.3
通讯作者：
Basrai, Munira A.
中科院分区：
文献类型：
--
作者：
Au, Wei-Chun;Crisp, Matthew J.;Basrai, Munira A.
Cse 4p是酿酒酵母中定义着丝粒身份的重要组蛋白H3变体，并且是染色体正确分离所需的。在这项研究中，我们研究了Cse 4p错误定位和组蛋白H3和Cse 4p剂量增加的表型后果，并建立了组蛋白化学计量，Cse 4p错误定位和染色体分离之间的直接联系。稳定的Cse 4p突变体Cse 4（K16 R）的过表达导致其错误定位，增加与染色质的关联，以及高的染色体丢失率，所有这些都被组蛋白H3（Delta 16 H3）的组成型表达抑制。我们确定Delta 16 H3不会导致染色体丢失增加;然而，增加组蛋白H3（GALH 3）的剂量会导致显著的染色体丢失，这是由于着丝粒突变体中着丝粒（CEN）相关的Cse 4p和合成剂量致死率（SDL）水平降低。这些表型被GALCSE 4抑制。我们得出结论，GALcse 4（K16 R）和GALH 3菌株的染色体错误分离是由于错误定位和功能受损的动粒，分别。组蛋白Delta 16 H3和GALCSE 4对这些表型的抑制支持了以下结论：适当的化学计量影响组蛋白H3和Cse 4p的定位，因此对于准确的染色体分离至关重要。
Cse4p is an essential histone H3 variant in Saccharomyces cerevisiae that defines centromere identity and is required for proper segregation of chromosomes. In this study, we investigated phenotypic consequences of Cse4p mislocalization and increased dosage of histone H3 and Cse4p, and established a direct link between histone stoichiometry, mislocalization of Cse4p, and chromosome segregation. Overexpression of the stable Cse4p mutant, cse4(K16R), resulted in its mislocalization, increased association with chromatin, and a high rate of chromosome loss, all of which were suppressed by constitutive expression of histone H3 (Delta 16H3). We determined that Delta 16H3 did not lead to increased chromosome loss; however, increasing the dosage of histone H3 (GALH3) resulted in significant chromosome loss due to reduced levels of centromere (CEN)-associated Cse4p and synthetic dosage lethality (SDL) in kinetochore mutants. These phenotypes were suppressed by GALCSE4. We conclude that the chromosome missegregation of GALcse4(K16R) and GALH3 strains is due to mislocalization and a functionally compromised kinetochore, respectively. Suppression of these phenotypes by histone Delta 16H3 and GALCSE4 supports the conclusion that proper stoichiometry affects the localization of histone H3 and Cse4p and is thus essential for accurate chromosome segregation.