Integrative and Functional Biology Unit, CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Institute of Biophysics of the CAS, v.v.i. Královopolská 135, 612 65 Brno, Czech Republic; Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, 91128 Palaiseau, France.
Trends Genet. 2023 Jan;39(1):59-73. doi: 10.1016/j.tig.2022.10.002. Epub 2022 Nov 17.
Although the impact of telomeres on physiology stands well established, a question remains: how do telomeres impact cellular functions at a molecular level? This is because current understanding limits the influence of telomeres to adjacent subtelomeric regions despite the wide-ranging impact of telomeres. Emerging work in two distinct aspects offers opportunities to bridge this gap. First, telomere-binding factors were found with non-telomeric functions. Second, locally induced DNA secondary structures called G-quadruplexes are notably abundant in telomeres, and gene regulatory regions genome wide. Many telomeric factors bind to G-quadruplexes for non-telomeric functions. Here we discuss a more general model of how telomeres impact the non-telomeric genome - through factors that associate at telomeres and genome wide - and influence cell-intrinsic functions, particularly aging, cancer, and pluripotency.
尽管端粒对生理学的影响已得到充分证实，但仍有一个问题悬而未决：端粒如何在分子水平上影响细胞功能？这是因为尽管端粒的影响广泛，但目前的理解将端粒的影响限制在相邻的亚端粒区域内。两个截然不同方面的新兴研究为弥合这一差距提供了机会。首先，发现了具有非端粒功能的端粒结合因子。其次，在端粒和整个基因组中，局部诱导的称为 G-四联体的 DNA 二级结构特别丰富。许多端粒因子结合 G-四联体以发挥非端粒功能。在这里，我们讨论了一个更一般的模型，即端粒如何通过与端粒和全基因组相关的因素来影响非端粒基因组，并影响细胞内在功能，特别是衰老、癌症和多能性。
