Melicher Dora, Buzas Edit I, Falus Andras
Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary.
Cell Mol Life Sci. 2015 Nov;72(21):4095-109. doi: 10.1007/s00018-015-1991-2. Epub 2015 Jul 20.
Telomeres are protective heterochromatic structures that cap the end of linear chromosomes and play a key role in preserving genomic stability. Telomere length represents a balance between processes that shorten telomeres during cell divisions with incomplete DNA replication and the ones that lengthen telomeres by the action of telomerase, an RNA-protein complex with reverse transcriptase activity which adds telomeric repeats to DNA molecule ends. Telomerase activity and telomere length have a crucial role in cellular ageing and in the pathobiology of several human diseases attracting intense research. The last few decades have witnessed remarkable advances in our understanding about telomeres, telomere-associated proteins, and the biogenesis and regulation of the telomerase holoenzyme complex, as well as about telomerase activation and the telomere-independent functions of telomerase. Emerging data have revealed that telomere length can be modified by genetic and epigenetic factors, sex hormones, reactive oxygen species and inflammatory reactions. It has become clear that, in order to find out more about the factors influencing the rate of telomere attrition in vivo, it is crucial to explore both genetic and epigenetic mechanisms. Since the telomere/telomerase assembly is under the control of multiple epigenetic influences, the unique design of twin studies could help disentangle genetic and environmental factors in the functioning of the telomere/telomerase system. It is surprising that the literature on twin studies investigating this topic is rather scarce. This review aims to provide an overview of some important immune response- and epigenetics-related aspects of the telomere/telomerase system demanding more research, while presenting the available twin data published in connection with telomere research so far. By emphasising what we know and what we still do not know in these areas, another purpose of this review is to urge more twin studies in telomere research.
端粒是一种保护性的异染色质结构,覆盖在线性染色体的末端,在维持基因组稳定性方面发挥着关键作用。端粒长度代表了细胞分裂过程中因DNA复制不完全而导致端粒缩短的过程与通过端粒酶作用使端粒延长的过程之间的平衡,端粒酶是一种具有逆转录酶活性的RNA-蛋白质复合物,可将端粒重复序列添加到DNA分子末端。端粒酶活性和端粒长度在细胞衰老以及几种人类疾病的病理生物学中起着至关重要的作用,吸引了大量研究。在过去几十年里,我们对端粒、端粒相关蛋白、端粒酶全酶复合物的生物发生和调控,以及端粒酶激活和端粒酶的非端粒依赖性功能的理解取得了显著进展。新出现的数据表明,端粒长度可被遗传和表观遗传因素、性激素、活性氧和炎症反应所改变。很明显,为了更深入了解体内影响端粒损耗速率的因素,探索遗传和表观遗传机制至关重要。由于端粒/端粒酶组装受多种表观遗传影响的控制,双胞胎研究的独特设计有助于厘清端粒/端粒酶系统功能中的遗传和环境因素。令人惊讶的是,关于这一主题的双胞胎研究文献相当稀少。本综述旨在概述端粒/端粒酶系统中一些与免疫反应和表观遗传学相关的重要方面,这些方面需要更多研究,同时呈现迄今为止与端粒研究相关的已发表的双胞胎数据。通过强调我们在这些领域已知和未知的内容,本综述的另一个目的是敦促在端粒研究中开展更多的双胞胎研究。