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端粒生物学——对一种有趣现象的洞察

Telomere Biology-Insights into an Intriguing Phenomenon.

作者信息

Venkatesan Shriram, Khaw Aik Kia, Hande Manoor Prakash

机构信息

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore, Singapore.

Clinical Research Unit, Khoo Teck Puat Hospital, 768828 Singapore, Singapore.

出版信息

Cells. 2017 Jun 19;6(2):15. doi: 10.3390/cells6020015.

Abstract

Bacteria and viruses possess circular DNA, whereas eukaryotes with typically very large DNA molecules have had to evolve into linear chromosomes to circumvent the problem of supercoiling circular DNA of that size. Consequently, such organisms possess telomeres to cap chromosome ends. Telomeres are essentially tandem repeats of any DNA sequence that are present at the ends of chromosomes. Their biology has been an enigmatic one, involving various molecules interacting dynamically in an evolutionarily well-trimmed fashion. Telomeres range from canonical hexameric repeats in most eukaryotes to unimaginably random retrotransposons, which attach to chromosome ends and reverse-transcribe to DNA in some plants and insects. Telomeres invariably associate with specialised protein complexes that envelop it, also regulating access of the ends to legitimate enzymes involved in telomere metabolism. They also transcribe into repetitive RNA which also seems to be playing significant roles in telomere maintenance. Telomeres thus form the intersection of DNA, protein, and RNA molecules acting in concert to maintain chromosome integrity. Telomere biology is emerging to appear ever more complex than previously envisaged, with the continual discovery of more molecules and interplays at the telomeres. This review also includes a section dedicated to the history of telomere biology, and intends to target the scientific audience new to the field by rendering an understanding of the phenomenon of chromosome end protection at large, with more emphasis on the biology of human telomeres. The review provides an update on the field and mentions the questions that need to be addressed.

摘要

细菌和病毒拥有环状DNA,而具有通常非常大的DNA分子的真核生物则必须进化为线性染色体,以规避如此大小的环状DNA超螺旋化的问题。因此,这类生物体拥有端粒来封闭染色体末端。端粒本质上是染色体末端存在的任何DNA序列的串联重复序列。它们的生物学特性一直是个谜,涉及各种分子以一种在进化中精心调整的方式动态相互作用。端粒的范围从大多数真核生物中的典型六聚体重复序列到难以想象的随机反转录转座子,后者在某些植物和昆虫中附着于染色体末端并反转录为DNA。端粒总是与包裹它的特殊蛋白质复合物相关联,这些复合物也调节染色体末端与参与端粒代谢的合法酶的接触。它们还转录为重复RNA,这似乎也在端粒维持中发挥着重要作用。因此,端粒形成了DNA、蛋白质和RNA分子协同作用以维持染色体完整性的交叉点。端粒生物学正呈现出比以前想象的更加复杂的态势,随着在端粒处不断发现更多的分子和相互作用。本综述还包括一个专门介绍端粒生物学历史的部分,旨在通过使广大读者对染色体末端保护现象有一个整体的理解,尤其是更多地关注人类端粒生物学,来针对该领域的新科学读者。该综述提供了该领域的最新情况,并提及了需要解决的问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb35/5492019/93d4cc6156e7/cells-06-00015-g001.jpg

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