著絲粒位于染色體上在細(xì)胞分裂過程中具有重要作用,，日前紐約大學(xué)的生物學(xué)家揭開了關(guān)鍵蛋白被裝入著絲粒的詳細(xì)機(jī)制,，有助于人們進(jìn)一步了解基因組復(fù)制并分析染色體數(shù)異常背后的潛在因素,。這項(xiàng)發(fā)現(xiàn)發(fā)表在最近一期的美國國家科學(xué)院院刊PNAS雜志上。
著絲粒負(fù)責(zé)介導(dǎo)染色體分離以確保子細(xì)胞獲得基因組的完整拷貝，這一過程遭到破壞可能導(dǎo)致染色體數(shù)異常,，而這種異常在90%的癌癥中都明顯存在。
研究人員利用裂殖酵母著重對著絲粒的結(jié)構(gòu)和功能進(jìn)行了研究。由于裂殖酵母的染色體復(fù)制和著絲粒調(diào)控與人類相似,，這種酵母是細(xì)胞生物學(xué)中常用的模式生物,。
在人類和裂殖酵母中都存在CENP-A蛋白，研究人員對這種蛋白在細(xì)胞分裂時(shí)期整合到著絲粒的過程進(jìn)行了研究,，以便更好的了解該蛋白在這一過程中的作用,。他們發(fā)現(xiàn)，在著絲粒復(fù)制時(shí)有三個(gè)蛋白Dos1,、Dos2和Cdc20共同起作用,，將CENP-A裝配到著絲粒中。進(jìn)一步研究顯示,，這一裝配過程遭到任何破壞,，都會使至關(guān)重要的CENP-A蛋白留在著絲粒以外，從而阻礙其執(zhí)行正常功能確保染色體正確分離,。
文章的資深作者是紐約大學(xué)生物學(xué)系的助理教授李飛（Fei Li音譯）,，他早年曾就讀于四川大學(xué)后到美國深造,，曾在Nature,、Cell等多家頂級期刊上發(fā)表文章。他解釋道,，CENP-A對于著絲粒功能至關(guān)重要，如果這種蛋白缺失著絲粒就無法行使功能,。此外,，他還指出許多類型的癌癥都與CENP-A的功能故障有關(guān),。“希望,，這些發(fā)現(xiàn)可以幫助人們開發(fā)更好的癌癥診斷和治療策略,。”他補(bǔ)充道,。(生物谷Bioon.com)
doi: 10.1073/pnas.1214874110
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Cell cycle-dependent deposition of CENP-A requires the Dos1/2–Cdc20 complex
Marlyn Gonzalez, Haijin He, Siyu Sun, Chen Li, and Fei Li1
Centromeric histone CENP-A, a variant of canonical histone H3, plays a central role in proper chromosome segregation. Loading of CENP-A at centromeres is cell cycle-regulated: parental CENP-A is deposited at centromeres during S phase, whereas newly synthesized CENP-A is deposited during later stages of the cell cycle. The mechanisms involved in deposition of CENP-A at centromeres during S phase remain poorly understood. In fission yeast, loading of CENP-A during S phase is regulated by the GATA-type factor, Ams2. Here we show that the Dos1/2-Cdc20 complex, previously characterized as a silencing complex essential for inheritance of H3K9 methylation during S phase, is also required for localization of CENP-Acnp1 at centromeres at this stage. Disruption of Dos1 (also known as Raf1/Clr8/Cmc1), Dos2 (also known as Raf2/Clr7/Cmc2), or Cdc20, a DNA polymerase epsilon subunit, results in dissociation of CENP-A from centromeres and mislocalization of the protein to noncentromeric sites. All three mutants display spindle disorganization and mitotic defects. Inactivation of Dos1 or Cdc20 also results in accumulation of noncoding RNA transcripts from centromeric cores, a feature common to mutants affecting kinetochore integrity. We further find that Dos1 physically associates with Ams2 and is required for the association of Ams2 with centromeric cores during S phase. Finally, we show that Dos2 associates with centromeric cores during S phase and that its recruitment to centromeric cores depends on Cdc20. This study identifies a physical link between DNA replication and CENP-A assembly machinery and provides mechanistic insight into how CENP-A is faithfully inherited during S phase.
