Loss of Rec8 from chromosome arm and centromere region is required for homologous chromosome separation and sister chromatid separation, respectively, in mammalian meiosis

Loss of Rec8 from chromosome arm and centromere region is required for homologous chromosome separation and sister chromatid separation, respectively, in mammalian meiosis
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DOI:
10.4161/cc.5.13.2903
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发表时间:
2006-07-01
期刊:
影响因子:
4.3
通讯作者:
Yamashita, Masakane
Yamashita, Masakane
中科院分区:
生物学3区
文献类型:
--
作者:
Lee, Jibak;Okada, Konosuke;Yamashita, Masakane

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减数分裂Ⅰ中的染色体分离与有丝分裂和减数分裂Ⅱ中的不同之处在于,前者是同源染色体彼此分离,而后者是姐妹篇染色体彼此分离。我们发现小鼠卵母细胞减数分裂特异性粘连蛋白亚基Rec 8显示出与酵母和哺乳动物精母细胞中报道的基本相同的定位模式; Rec 8沿着染色体臂(armRec 8)在中期I到后期I的过渡中丢失,尽管着丝粒Rec 8(cenRec 8)保持到后期II的开始。通过将抗Rec 8抗体显微注射到卵母细胞中来抑制armRec 8的损失抑制同源物分离,但不抑制第一极体发射(胞质分裂)。类似地,将抗Rec 8抗体注射到中期II卵母细胞中防止卵母细胞活化后后期II中的姐妹分离。这些数据表明,armRec 8和cenRec 8的损失是需要分离的同源物和姐妹篇,分别,但都不需要其他晚期有丝分裂事件,如纺锤体伸长和小鼠卵母细胞胞质分裂。此外,通过使用一些纺锤体组装,蛋白酶体和拓扑异构酶II和Securin的过表达的抑制剂,我们提出,armRec 8(同源分离)的损失和胞质分裂被抑制,直到后期I由Securin的破坏调节纺锤体检查点-蛋白酶体途径,和拓扑异构酶II是必需的同源分离独立于这样的途径。
Chromosome separation in meiosis I is different from those in mitosis and meiosis II in that homologs separate from each other in the former while sisters do so in the latter. We show here that meiosis-specific cohesin subunit Rec8 in mouse oocytes shows essentially the same pattern of localization to those reported in yeasts and mammalian spermatocytes; Rec8 along chromosome arm ( armRec8) is lost at the metaphase I-to-anaphase I transition, although centromeric Rec8 (cenRec8) is maintained until the onset of anaphase II. Suppression of the loss of armRec8 by microinjection of anti-Rec8 antibody into the oocytes inhibits homolog separation but not the first polar body emission ( cytokinesis). Similarly, the injection of anti-Rec8 antibody into metaphase II oocytes prevents sister separation in anaphase II after oocyte activation. These data demonstrate that the loss of armRec8 and cenRec8 is required for separation of homologs and sisters, respectively, but both are not required for other late mitotic events such as spindle elongation and cytokinesis in mouse oocytes. Further, by using some inhibitors for spindle assembly, proteasome and Topoisomerase II and overexpression of Securin, we propose that loss of armRec8 ( homolog separation) and cytokinesis are suppressed until anaphase I by Securin whose destruction is regulated by spindle checkpoint-proteasome pathway, and that Topoisomerase II is required for homolog separation independently from such pathway.