Mutation of YCS4, a budding yeast condensin subunit, affects mitotic and nonmitotic chromosome behavior

Mutation of YCS4, a budding yeast condensin subunit, affects mitotic and nonmitotic chromosome behavior
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DOI:
10.1091/mbc.01-05-0264
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发表时间:
2002-02-01
影响因子:
3.3
通讯作者:
Murray, AW
Murray, AW
中科院分区:
生物学3区
文献类型:
--
作者:
Bhalla, N;Biggins, S;Murray, AW

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发芽酵母YCS4基因编码凝集素复合体的一个保守的调节亚基。我们在筛选姐妹染色单体分离或分离缺陷的突变体时,分离了该基因的一个等位基因。Ycs4-1突变体的表型类似于拓扑异构酶11突变体,而不同于ESP1-1突变体:尽管正常地从有丝分裂染色体上去除粘附素,但ycs4-1中姐妹染色单体的拓扑分辨率受到了影响。与姐妹分离中的作用一致,YCS4的功能需要将DNA拓扑异构酶I和II定位到染色体上。与非洲爪哇和分裂酵母中的同源物不同,Ycs4p在整个细胞周期中与染色质相关;唯一的定位变化发生在蛋白质在核仁浓缩的后期。这种重新定位可能揭示了在有丝分裂过程中,分离转录上高度活跃的、重复的rDNA基因阵列所面临的特殊挑战。确实,在不允许的温度下,ycs4-1的核仁分离是异常的。在允许的温度下,rDNA阵列中的重复间重组在ycs4-1中被特异性地提高,这表明Ycs4p除了在其分离之外,还在阵列中发挥作用。此外,在容许温度下,ycs4-1在交配型基因座上存在沉默缺陷。综上所述,我们的数据表明,在萌芽酵母中,存在与凝集素功能丧失相关的有丝分裂和非有丝分裂染色体异常。
The budding yeast YCS4 gene encodes a conserved regulatory subunit of the condensin complex. We isolated an allele of this gene in a screen for mutants defective in sister chromatid separation or segregation. The phenotype of the ycs4-1 mutant is similar to topoisomerase 11 mutants and distinct from the esp1-1 mutant: the topological resolution of sister chromatids is compromised in ycs4-1 despite normal removal of cohesins from mitotic chromosomes. Consistent with a role in sister separation, YCS4 function is required to localize DNA topoisomerase I and II to chromosomes. Unlike its homologs in Xenopus and fission yeast, Ycs4p is associated with chromatin throughout the cell cycle; the only change in localization occurs during anaphase when the protein is enriched at the nucleolus. This relocalization may reveal the specific challenge that segregation of the transcriptionally hyperactive, repetitive array of rDNA genes can present during mitosis. Indeed, segregation of the nucleolus is abnormal in ycs4-1 at the nonpermissive temperature. Interrepeat recombination in the rDNA array is specifically elevated in ycs4-1 at the permissive temperature, suggesting that the Ycs4p plays a role at the array aside from its segregation. Furthermore, ycs4-1 is defective in silencing at the mating type loci at the permissive temperature. Taken together, our data suggest that there are mitotic as well as nonmitotic chromosomal abnormalities associated with loss of condensin function in budding yeast.