共查询到17条相似文献,搜索用时 31 毫秒
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端粒是真核细胞染色体末端的特有结构,是由端粒结合蛋白和一段重复序列的端粒DNA组成的一个高度精密的复合体,在维持染色体末端稳定性,避免染色体被核酸酶降解等方面起着重要的作用。端粒的长度、结构及组织形式受多种端粒结合因子的调控。由于端粒的重要性,在哺乳动物细胞里,端粒的长度或端粒结构变化与癌症发生及细胞衰老有密切的关系。由于末端复制问题的存在,随着细胞分裂次数的增加,端粒不断缩短,细胞不可避免的走向衰老或凋亡。由于在细胞分裂过程中端粒长度的不断缩短与细胞分裂代数增加具有相关性,即端粒长度反应了细胞的分裂次数,因此有人将端粒形象的比喻为生物时钟。在90%的癌细胞中,端粒酶被重新激活,以此来维持端粒的长度,使细胞走向永生化。简要综述了端粒、端粒酶及端粒酶结合蛋白的最新研究进展。 相似文献
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重点讨论了端粒酶在肿瘤细胞和永生化细胞中的作用和功能,以及它与细胞衰老和永生化的关系.多数真核细胞的端粒酶能将单一重复序列加到端粒DNA的3′末端.端粒酶主要由模板RNA和端粒酶蛋白催化亚基组成,后者以前者为模板起逆转录酶的作用.端粒酶活性存在于肿瘤细胞中,而在良性肿瘤、体细胞中未发现端粒酶. 相似文献
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细胞分裂中染色体因其末端(端粒)的DNA不能完全复制而短缩,使细胞逐渐失去增殖能力而衰老.端粒酶可延长染色体末端DNA,端粒酶的活化使细胞无限增殖.85%左右的恶性肿瘤端粒酶表达阳性,生殖细胞和无限繁殖的细胞系中端粒酶表达也呈阳性.文章综述了端粒的构成和功能、端粒酶在端粒合成中的作用,介绍了端粒酶活性的测定方法、细胞恶变与端粒酶激活的关系,并论及通过抑制端粒酶活性来治疗癌症的可能性. 相似文献
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端粒、端粒酶分子生物学研究进展 总被引:2,自引:0,他引:2
随着端粒、端粒酶研究工作的广泛开展,人们已逐步认识到它们与衰老、癌症发生过程中的许多重要的生物学现象相关。因此端粒、端粒酶已成为生命科学研究的一个热点。本文总结了近年来有关端粒、端粒酶的结构和功能及端粒长度、端粒酶活性调节机制的研究进展。 相似文献
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端粒、端粒酶结构功能研究进展 总被引:1,自引:0,他引:1
端粒是真核生物线性染色体末端由重复DNA序列和蛋白质结合形成的复合结构,其特殊的环形结构与多种结合蛋白形成了端粒的多重功能的基础。端粒的功能包括染色体末端的保护、引导减数分裂的同源染色体配对、参与DNA修复过程等;端粒酶具有逆转录酶特性和维持端粒长度的功能,其活性与恶性肿瘤的发生密切相关,调控因子错综复杂。 相似文献
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Peili Gu Shuting Jia Taylor Takasugi Eric Smith Jayakrishnan Nandakumar Eric Hendrickson Sandy Chang 《Aging cell》2018,17(4)
Coats plus (CP) is a rare autosomal recessive disorder caused by mutations in CTC1, a component of the CST (CTC1, STN1, and TEN1) complex important for telomere length maintenance. The molecular basis of how CP mutations impact upon telomere length remains unclear. The CP CTC1L1142H mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and RPE cells to demonstrate that CTC1:STN1 interaction is required to repress telomerase activity. CTC1L1142H interacts poorly with STN1, leading to telomerase‐mediated telomere elongation. Impaired interaction between CTC1L1142H:STN1 and DNA Pol‐α results in increased telomerase recruitment to telomeres and further telomere elongation, revealing that C:S binding to DNA Pol‐α is required to fully repress telomerase activity. CP CTC1 mutants that fail to interact with DNA Pol‐α resulted in loss of C‐strand maintenance and catastrophic telomere shortening. Our findings place the CST complex as an important regulator of both G‐strand extensions by telomerase and C‐strand synthesis by DNA Pol‐α. 相似文献
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Gomes NM Ryder OA Houck ML Charter SJ Walker W Forsyth NR Austad SN Venditti C Pagel M Shay JW Wright WE 《Aging cell》2011,10(5):761-768
Progressive telomere shortening from cell division (replicative aging) provides a barrier for human tumor progression. This program is not conserved in laboratory mice, which have longer telomeres and constitutive telomerase. Wild species that do/do not use replicative aging have been reported, but the evolution of different phenotypes and a conceptual framework for understanding their uses of telomeres is lacking. We examined telomeres/telomerase in cultured cells from > 60 mammalian species to place different uses of telomeres in a broad mammalian context. Phylogeny‐based statistical analysis reconstructed ancestral states. Our analysis suggested that the ancestral mammalian phenotype included short telomeres (< 20 kb, as we now see in humans) and repressed telomerase. We argue that the repressed telomerase was a response to a higher mutation load brought on by the evolution of homeothermy. With telomerase repressed, we then see the evolution of replicative aging. Telomere length inversely correlated with lifespan, while telomerase expression co‐evolved with body size. Multiple independent times smaller, shorter‐lived species changed to having longer telomeres and expressing telomerase. Trade‐offs involving reducing the energetic/cellular costs of specific oxidative protection mechanisms (needed to protect < 20 kb telomeres in the absence of telomerase) could explain this abandonment of replicative aging. These observations provide a conceptual framework for understanding different uses of telomeres in mammals, support a role for human‐like telomeres in allowing longer lifespans to evolve, demonstrate the need to include telomere length in the analysis of comparative studies of oxidative protection in the biology of aging, and identify which mammals can be used as appropriate model organisms for the study of the role of telomeres in human cancer and aging. 相似文献
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