人端粒酶活性的调控机制及其新功能研究进展

端粒酶活性在胚胎发育过程中消失,人的绝大多数体细胞没有端粒酶活性,因而随着体细胞分裂次数的增加,端粒长度在不断缩短.当端粒缩短到一定程度时,细胞无法维持正常的端粒结构而导致细胞的衰老,而当细胞衰老调控机制失控的情况下,端粒的极限缩短将导致细胞死亡或癌变.端粒酶的活性在细胞癌变的过程中被重新激活以维持端粒的长度和结构,以及细胞无限增殖化的能力,与衰老及肿瘤的发生发展密.切相关.随着人们对端粒酶认识的深入,新研究进展显示端粒酶具有独立于端粒之外的新功能,端粒酶在DNA修复、促进细胞存活、基因转录及刺激干细胞增殖等方面不依赖于端粒的新功能的发现,为阐明端粒酶在衰老及癌变中重要功能的分子机制提供了新的思路.

Regulation of Telomerase and Its Actions beyond Telomeres

Most human somatic cells have undetectable telomerase activity due to repression during early embryonic development.Consequently human somatic cells lose telomeric DNA after each round of replication.When telomeres become critically shortened,the protective function of the telomere is compromised and ultimately leads to cellular senescence.However,when cellular mechanism of senescence is inactivated,critically shortened telomeres may induce cell death and immortalization.Telomerase activity is reactivated during cellular immortalization and has fundamental roles in bypassing cellular aging and in cancer progression by maintaining telomere homeostasis and integrity.Recent studies suggest novel biochemical properties of telomerase in several essential cell signaling pathways without apparent involvement of its well established function in telomere maintenance.The findings of extracurricular activities of telomerase in apoptosis,DNA repair,stem cell function,and in the regulation of gene expression may further enhance our understanding of the molecular actions of telomerase in aging and cancer.