SUMO修饰与端粒维持

端粒(telomere)长度维持在一定的范围内是细胞正常生理功能的一个重要的基础,端粒长度的变化可导致两个截然相反的病理生理过程-癌变和衰老,端粒过长可引起细胞永生化而癌变,端粒进行性缩短则有丝分裂能力下降导致细胞衰老1].端粒的长度和结构依赖端粒酶的活性及端粒蛋白复合体(shelterin)的调节2],端粒酶的激活可引起端粒DNA序列增加而延长细胞的寿命.泛素样小分子修饰(small ubiquin-like modifier,SUMO修饰)在不同的端粒维持机制中的作用途径不同,SUMO修饰可激活端粒酶的活性,促进依赖端粒酶合成端粒的途径,SUMO修饰也可促进同源重组途径合成端粒的能力3],增加端粒的长度,在保持端粒的长度上发挥重要的调节作用.

Effect of SUMOylation on maintenance of telomere

Telomeres are the unique structure at the end of chromosomes, which pose two special challenges for the cellular DNA replication and repair machinery. Because of the inability of lagging strand synthesis to fully replicate a linear template, the chromosome ends is progressively shortening at each replication cycle. The tandem DNA repeats must maintain enough length to allow the cell dividing and mitosing, otherwise the cells would lose the dividing ability and undergo replicative senescence. There are two special pathways to regulate telomere length, which consist of telomerase and alternative lengthening of telomeres (ALT). SUMO is an evolutionarily conserved protein, which is covalently attached to target proteins and alters their conformation, stability, interaction and localization. Currently, a lot of proteins have been proved to be the substrates of SUMOylation. A growing body of evidence implicate that SUMOylation plays a very important role to elongate telomeres in both telomerase and ALT. The Rad5 and Rad52, as well as BLM have been showed either to be modified by SUMO or to interact with SUMO. SUMOylation positively modifies the activity of telomere.