啤酒酵母复制衰老的分子机制  

Molecular Mechanism of Replicative Aging Regulation in Saccharomyces cerevisiae

作　　者：易宗春[1] 孙艳[1] 庄逢源[1] 

机构地区：[1]北京航空航天大学生物工程系,北京100083

出　　处：《中国生物化学与分子生物学报》2007年第3期181-186,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No30400092)资助~~

摘　　要：复制衰老是啤酒酵母衰老形式之一,表现出芽痕累积、细胞体积变大、不对称分裂丧失、不育、核仁脆裂和代谢变化等特征.染色体外rDNA环累积是啤酒酵母复制衰老的重要原因,而组蛋白去乙酰化酶家族成员Sir2蛋白在调节染色体外rDNA环累积、啤酒酵母衰老和寿命方面起到核心作用.作为去乙酰化反应底物的NAD+正性调节Sir2组蛋白去乙酰化酶活性,NAD+代谢产物尼克酰胺对Sir2有负性调节作用,而有尼克酰胺参与的NAD+补救合成途径对于Sir2活性十分重要.目前,已经在人等动物细胞中发现参与这些调节过程的相关蛋白的同源基因,在功能上也表现出一定的相似性.啤酒酵母的衰老机制研究将为人体衰老的认识提供重要线索.Replicative aging is one of aging forms in Saccharomyces cerevisiae. Replicatively aged cells show characteristics including bud scar accumulation, increased cell size, loss of asymmetry and fertility, nucleolar fragmentation, and metabolic changes. Extracromosomal rDNA circles （ERCs） accumulation is a major cause of yeast replicative aging, which is regulated by NAD~ -dependant histone deacetylase Sir2. NAD^＋ regulates Sir2 histone deacetylase activity, which is consumed in Sir2-catalyzed deacetylation reaction as a substrate. Nicotinamide, NAD^＋ metabolic product in this reaction, is a strong inhibitor of Sir2. Salvage synthesis of NAD^＋ is critical for Sir2 activity, which is one pathway of nicotinamide metabolism. Homologues of genes involved in regulation of this reaction have been found in mammal cells with similar functions. Therefore, definition of molecular mechanism of yeast replicative aging regulation will be attributed to expose human aging.

关 键 词：复制衰老 染色体外rDNA环 Sir2组蛋白去乙酰化酶 NAD^+ 

分 类 号：Q756[生物学—分子生物学]