Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich, Switzerland.
Nucleus. 2012 Jan-Feb;3(1):16-21. doi: 10.4161/nucl.18929.
The human helicase and ATPase up-frameshift suppressor 1 (UPF1), traditionally known as a major player in several RNA quality control mechanisms, is emerging as a crucial caretaker of the stability of the genome. Work from my laboratory has provided insight into the function of UPF1 during DNA metabolism and has revealed that this versatile enzyme sustains the proper replication of telomeres, the protective structures located at the ends of linear eukaryotic chromosomes. We have supplied direct evidence that telomere replication is not completed in cells with compromised UPF1 function, leading to the accumulation of DNA damage and telomere abnormalities. We also have isolated a number of factors that physically interact with UPF1 and might represent molecular links between UPF1 and telomeres. In this paper, I re-evaluate the functions of UPF1 in maintaining the stability of telomeres and of the genome at large and suggest a model that explains how UPF1 might be recruited and function during telomere replication.
人类解旋酶和 ATP 酶上移框抑制因子 1（UPF1），传统上被认为是几种 RNA 质量控制机制的主要参与者，它正在成为基因组稳定性的关键维护者。我的实验室的工作提供了 UPF1 在 DNA 代谢过程中的功能的深入了解，并揭示了这种多功能酶维持端粒的适当复制，端粒是位于线性真核染色体末端的保护结构。我们提供了直接的证据表明，在 UPF1 功能受损的细胞中，端粒复制没有完成，导致 DNA 损伤和端粒异常的积累。我们还分离了一些与 UPF1 相互作用的因子，这些因子可能代表 UPF1 和端粒之间的分子联系。在本文中，我重新评估了 UPF1 在维持端粒和整个基因组稳定性方面的功能，并提出了一个模型，解释了 UPF1 如何在端粒复制过程中被招募和发挥作用。
