A MUTATION IN CSE4, AN ESSENTIAL GENE ENCODING A NOVEL CHROMATIN-ASSOCIATED PROTEIN IN YEAST, CAUSES CHROMOSOME NONDISJUNCTION AND CELL-CYCLE ARREST AT MITOSIS

A MUTATION IN CSE4, AN ESSENTIAL GENE ENCODING A NOVEL CHROMATIN-ASSOCIATED PROTEIN IN YEAST, CAUSES CHROMOSOME NONDISJUNCTION AND CELL-CYCLE ARREST AT MITOSIS
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DOI:
10.1101/gad.9.5.573
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发表时间:
1995-03-01
影响因子:
10.5
通讯作者:
FITZGERALDHAYES, M
FITZGERALDHAYES, M
中科院分区:
生物学1区
文献类型:
--
作者:
STOLER, S;KEITH, KC;FITZGERALDHAYES, M

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着丝粒是真核生物染色体上的一个分化区域,在有丝分裂中介导姐妹染色单体的分离。在这项研究中,酿酒酵母染色体误分离突变体,cse4 - 1,已被分离,并显示出增加不分离频率的染色体携带突变着丝粒DNA序列。此外,在升高的温度下,cse4 - 1等位基因引起有丝分裂特异性停滞,主要是含有单个G(2)核和短双极有丝分裂纺锤体的大出芽细胞。野生型基因CSE 4是细胞分裂所必需的,编码的蛋白质含有与高度保守的染色质蛋白组蛋白H3 64%相同的结构域。生物化学实验表明,CSE 4p具有与组蛋白113相似的DNA结合特性,并可能在体内形成特化的核小体结构。有趣的是,人类着丝粒蛋白CENP-A也含有这种H3样结构域。这里提供的数据表明,CSE4p是所需的适当的动粒功能在酵母中,并可能代表一个进化上保守的蛋白质组装所必需的独特的染色质结构与真核着丝粒。
The centromere, a differentiated region of the eukaryotic chromosome, mediates the segregation of sister chromatids at mitosis. In this study, a Saccharomyces cerevisiae chromosome mis-segregation mutant, cse4-1, has been isolated and shown to increase the nondisjunction frequency of a chromosome bearing a mutant centromere DNA sequence. In addition, at elevated temperatures the cse4-1 allele causes a mitosis-specific arrest with a predominance of large budded cells containing single G(2) nuclei and short bipolar mitotic spindles. The wild-type gene, CSE4, is essential for cell division and encodes a protein containing a domain that is 64% identical to the highly conserved chromatin protein, histone H3. Biochemical experiments demonstrate that CSE4p has similar DNA binding characteristics as those of histone 113 and might form a specialized nucleosome structure in vivo. Interestingly, the human centromere protein, CENP-A, also contains this H3-like domain. Data presented here indicate that CSE4p is required for proper kinetochore function in yeast and may represent an evolutionarily conserved protein necessary for assembly of the unique chromatin structure associated with the eukaryotic centromere.