黑腹果蝇dCAF-1-p55突变引起果蝇发育迟缓和染色体不稳定性(英文)  

dCAF-1-p55 is Essential for Drosophila Development and Involved in The Maintenance of Chromosomal Stability

作　　者：吴青华[1,2] 刘继勇[1] 陈毅序[1] 焦仁杰[1] 

机构地区：[1]中国科学院生物物理研究所,脑与认知国家重点实验室,北京100101 [2]中国科学院大学,北京100049

出　　处：《生物化学与生物物理进展》2012年第11期1073-1081,共9页Progress In Biochemistry and Biophysics

基　　金：supported by grants from The National Natural Science Foundation of China(31071087,31100889);National Basic Research Program of China(2009CB918702)~~

摘　　要：在真核生物中高度保守的染色质装配因子1(chromatin assembly factor 1,CAF-1)是染色质装配过程中的组蛋白分子伴侣之一.dCAF-1-p55是果蝇中CAF-1复合物中的最小亚基,它与另外两个亚基dCAF-1-p180及dCAF-1-p105一起负责将组蛋白H3/H4组装到新合成的DNA上.除了CAF-1复合物,dCAF-1-p55还参与其他多个复合物的形成,如NURF、PRC2及Sin3-HDAC1.dCAF-1-p55的这一广泛参与性提示了其功能的多样性和重要性.为了研究dCAF-1-p55的体内功能,我们利用基因靶向敲除技术制备了果蝇dCAF-1-p55突变体.实验结果表明,dCAF-1-p55的缺失导致果蝇发育迟缓并且最终致死.进一步研究发现,在dCAF-1-p55突变细胞中,中期染色体较为松散,姐妹染色单体连接异常,后期染色体不能正常分离.这些缺陷都是与癌症发生密切相关的染色体不稳定性(chromosome instability,CIN)的典型特征.综上所述,我们的研究表明了dCAF-1-p55在果蝇发育过程及维持染色体稳定性方面的重要作用,同时提示该基因具有保护细胞免遭CIN和癌变的潜在功能.The chromatin assembly factor 1 （CAF-1） is a three-subunit protein complex that functions in chaperoning histone deposition. The smallest subunit of Drosophila CAF-1, dCAF-l-p55, together with the other two subunits dCAF-I-pl80 and dCAF-I-pl05, participates in the deposition of histone H3 and H4 onto the newly synthesized DNA. In addition to the CAF-1 complex, dCAF-l-p55 is also found in several other complexes such as NURF, PRC2 and Sin3-HDAC1 complex, suggesting that it plays multiple roles other than a historic chaperone. Here we report a new allele of dCA F-l-p55 generated by gene targeting. We show that dCAF-l-p55 loss-of-function led to developmental delay and lethality. Further investigations demonstrated that dCAF-l-p55 deficient cells exhibited defects in metaphase chromosome condensation, sister chromatids association and anaphase chromosomes segregation, which are premonitory signs of chromosome instability （C1N）. Taken together, these results indicate that dCAF-l-p55 plays a role in the maintenance of chromosomal stability, likely to protect the cells from CIN and the proneness to cancer.

关 键 词：果蝇 dCAF-1-p55 染色体不稳定性 染色体分离 姐妹染色单体连接 

分 类 号：Q344[生物学—遗传学] Q969.462.2