着丝粒位于染色体上在细胞分裂过程中具有重要作用，日前纽约大学的生物学家揭开了关键蛋白被装入着丝粒的详细机制，有助于人们进一步了解基因组复制并分析染色体数异常背后的潜在因素。这项发现发表在最近一期的美国国家科学院院刊PNAS杂志上。
着丝粒负责介导染色体分离以确保子细胞获得基因组的完整拷贝，这一过程遭到破坏可能导致染色体数异常，而这种异常在90%的癌症中都明显存在。
研究人员利用裂殖酵母着重对着丝粒的结构和功能进行了研究。由于裂殖酵母的染色体复制和着丝粒调控与人类相似，这种酵母是细胞生物学中常用的模式生物。
在人类和裂殖酵母中都存在CENP-A蛋白，研究人员对这种蛋白在细胞分裂时期整合到着丝粒的过程进行了研究，以便更好的了解该蛋白在这一过程中的作用。他们发现，在着丝粒复制时有三个蛋白Dos1、Dos2和Cdc20共同起作用，将CENP-A装配到着丝粒中。进一步研究显示，这一装配过程遭到任何破坏，都会使至关重要的CENP-A蛋白留在着丝粒以外，从而阻碍其执行正常功能确保染色体正确分离。
文章的资深作者是纽约大学生物学系的助理教授李飞（Fei Li音译），他早年曾就读于四川大学后到美国深造，曾在Nature、Cell等多家顶级期刊上发表文章。他解释道，CENP-A对于着丝粒功能至关重要，如果这种蛋白缺失着丝粒就无法行使功能。此外，他还指出许多类型的癌症都与CENP-A的功能故障有关。“希望，这些发现可以帮助人们开发更好的癌症诊断和治疗策略。”他补充道。(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.
