ALT—— 端粒延长替代机制 - 遗传.PDF

HEREDITAS (Beijing) 2009 12 , 31(12): 1185―1191 ISSN 0253-9772 综 述 DOI: 10.3724/SP.J.1005.2009.01185 ALT——端粒延长替代机制 吴晓明, 唐文如, 罗瑛 , 650224 端粒长度和结构的稳定与肿瘤及衰老的发生密切相关, 端粒维持机制是细胞增殖的必要条件, 端粒维持 机制的激活是肿瘤细胞演化过程中的一个重要环节。这种端粒维持机制可能是通过重新激活端粒酶, 使细胞快 速增殖。在端粒酶失活或不足的情况下, 也存在着一种或多种维持和增加端粒长度的机制, 统称为端粒延长替 代机制(Alterative lengthening of telomere, ALT) 。其特点包括: 具有不均一的端粒长度, 存在与ALT 相关的PML 小体(APBs) 以及同源重组增加。ALT 细胞内存在的ALT 相关蛋白及异常活跃的同源重组为ALT 机制的激活和 维持提供了可能。文章综述了ALT 的特征性表型、与端粒酶的相关性及其可能的发生机制。对ALT 机制的深 入研究将有利于阐明衰老与肿瘤之间的辩证关系。 端粒延长替代机制; 与ALT 相关的PML 小体; 同源重组; 端粒蛋白复合体; 端粒 ALT——Alternative lengthening of telomere WU Xiao-Ming, TANG Wen-Ru, LUO Ying Lab of Molecular Genetics of Aging and Tumor, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650224, China Abstract: The maintenance of the length and normal structure of telomeres is highly related to the development of senes- cence and tumorigenesis. The mechanisms of maintaining telomere are essential for cell growth and the reactivation of these mechanisms is an important step in tumor progression. The mechanism of telomere maintenance might be the reactivation of telomerase. In the case of telomerase deficiency, the mechanisms for maintaining the lengths of telomeres are referred to as alternative lengthening of telomere (ALT). The characteristics of the ALT cells include great heterogeneity of telomere size in individual cells, ALT-associated PML (promyelocytic leukemia) bodies, and evident homologous recombination. The ALT-related proteins and elevated homologous recombination found in ALT cells provide a possible mechanism for the alternative lengthening of telomere. The study o