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端粒与衰老。

Telomeres and aging.

机构信息

Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9039, USA.

出版信息

Curr Opin Cell Biol. 2018 Jun;52:1-7. doi: 10.1016/j.ceb.2017.12.001. Epub 2017 Dec 15.

Abstract

Telomeres (the TTAGGG repetitive DNA at the ends of linear chromosomes) are part of the 3D spatial organization of the nuclear genome. Long-range 3D chromatin interactions also establish specific patterns of regulated gene expression. An emerging area of interest is the role of telomere 3D looping with interstitial telomeric sequences (ITS) through interactions with telomere shelterin proteins. Telomeres form interstitial telomere loops (ITL) that interact with ITS and modify gene expression at distal genomic regions. Human laminopathies and telomeropathies often correlate with short telomeres. Since telomeres progressively shorten with increased turnover and chronological age in dividing somatic cells, ITLs may also change and have functional roles in normal and pathophysiological processes. Overall, telomeres help stabilize the nuclear genome with high fidelity throughout early adult life but diminish in post-reproductive age-associated pathology.

摘要

端粒(线性染色体末端的 TTAGGG 重复 DNA)是核基因组 3D 空间结构的一部分。长程 3D 染色质相互作用也建立了特定的调节基因表达模式。一个新兴的研究领域是端粒 3D 环与间隔端粒序列(ITS)的作用,通过与端粒庇护蛋白的相互作用。端粒形成间隔端粒环(ITL),与 ITS 相互作用,并修饰远端基因组区域的基因表达。人类层粘连蛋白病和端粒体病常与短端粒相关。由于端粒在有丝分裂体细胞中随着周转率和年龄的增加而逐渐缩短,因此 ITL 也可能发生变化,并在正常和病理生理过程中发挥功能作用。总的来说,端粒在整个成年早期帮助高度忠实稳定核基因组,但在与生殖后相关的病理中减少。

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