Hall Ira M, Noma Ken-Ichi, Grewal Shiv I S
Watson School of Biological Sciences, Cold Spring Harbor Laboratory, P.O. Box 100, NY 11724, USA.
Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):193-8. doi: 10.1073/pnas.232688099. Epub 2002 Dec 30.
The regulation of higher-order chromosome structure is central to cell division and sexual reproduction. Heterochromatin assembly at the centromeres facilitates both kinetochore formation and sister chromatid cohesion, and the formation of specialized chromatin structures at telomeres serves to maintain the length of telomeric repeats, to suppress recombination, and to aid in formation of a bouquet-like structure that facilitates homologous chromosome pairing during meiosis. In fission yeast, genes encoding the Argonaute, Dicer, and RNA-dependent RNA polymerase factors involved in RNA interference (RNAi) are required for heterochromatin formation at the centromeres and mating type region. In this study, we examine the effects of deletions of the fission yeast RNAi machinery on chromosome dynamics during mitosis and meiosis. We find that the RNAi machinery is required for the accurate segregation of chromosomes. Defects in mitotic chromosome segregation are correlated with loss of cohesin at centromeres. Although the telomeres of RNAi mutants maintain silencing, length, and localization of the heterochromatin protein Swi6, we discovered defects in the proper clustering of telomeres in interphase mitotic cells. Furthermore, a small proportion of RNAi mutant cells display aberrant telomere clustering during meiotic prophase. This study demonstrates that the fission yeast RNAi machinery is required for the proper regulation of chromosome architecture during mitosis and meiosis.
高阶染色体结构的调控对于细胞分裂和有性生殖至关重要。着丝粒处的异染色质组装有助于动粒形成和姐妹染色单体黏连，而端粒处特殊染色质结构的形成则有助于维持端粒重复序列的长度、抑制重组，并有助于形成一种花束样结构，促进减数分裂过程中同源染色体配对。在裂殖酵母中，参与RNA干扰（RNAi）的编码Argonaute、Dicer和RNA依赖性RNA聚合酶因子的基因是着丝粒和交配型区域异染色质形成所必需的。在本研究中，我们研究了裂殖酵母RNAi机制缺失对有丝分裂和减数分裂过程中染色体动态变化的影响。我们发现RNAi机制是染色体精确分离所必需的。有丝分裂染色体分离缺陷与着丝粒处黏连蛋白的丢失相关。尽管RNAi突变体的端粒维持了异染色质蛋白Swi6的沉默、长度和定位，但我们发现有丝分裂间期细胞中端粒的正确聚集存在缺陷。此外，一小部分RNAi突变体细胞在减数分裂前期显示出异常的端粒聚集。这项研究表明，裂殖酵母RNAi机制是有丝分裂和减数分裂过程中染色体结构正确调控所必需的。
