Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
FEBS Lett. 2010 Sep 10;584(17):3760-72. doi: 10.1016/j.febslet.2010.07.007. Epub 2010 Jul 14.
Telomeres protect the ends of eukaryotic chromosomes from being recognized and processed as double strand breaks. In most organisms, telomeric DNA is highly repetitive with a high GC-content. Moreover, the G residues are concentrated in the strand running 3'-5' from the end of the chromosome towards its center. This G-rich strand is extended to form a 3' single-stranded tail that can form unusual secondary structures such as T-loops and G-quadruplex DNA. Both the duplex repeats and the single-stranded G-tail are assembled into stable protein-DNA complexes. The unique architecture, high GC content, and multi-protein association create particularly stable protein-DNA complexes that are a challenge for replication, recombination, and transcription. Helicases utilize the energy of nucleotide hydrolysis to unwind base paired nucleic acids and, in some cases, to displace proteins from them. The telomeric functions of helicases from the RecQ, Pifl, FANCJ, and DNA2 families are reviewed in this article. We summarize data showing that perturbation of their telomere activities can lead to telomere dysfunction and genome instability and in some cases human disease.
端粒保护真核染色体的末端不被识别和处理为双链断裂。在大多数生物体中，端粒 DNA 高度重复，GC 含量高。此外，G 残基集中在从染色体末端向其中心延伸的 3' 到 5' 链上。这条富含 G 的链延伸形成 3' 单链尾巴，可以形成异常的二级结构，如 T 环和 G-四链体 DNA。双链重复序列和单链 G 尾都组装成稳定的蛋白-DNA 复合物。独特的结构、高 GC 含量和多蛋白缔合形成了特别稳定的蛋白-DNA 复合物，这对复制、重组和转录都是一个挑战。解旋酶利用核苷酸水解的能量解开碱基配对的核酸，在某些情况下，从核酸上置换蛋白质。本文综述了 RecQ、Pifl、FANCJ 和 DNA2 家族的解旋酶的端粒功能。我们总结了数据表明，它们的端粒活性受到干扰会导致端粒功能障碍和基因组不稳定，在某些情况下还会导致人类疾病。
