Department of Biology, University of Iowa, Iowa City, IA 52242, USA.
Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USA.
Biomolecules. 2024 Jan 16;14(1):113. doi: 10.3390/biom14010113.
Alternative lengthening of telomeres (ALT) is a homologous recombination-based pathway utilized by 10-15% of cancer cells that allows cells to maintain their telomeres in the absence of telomerase. This pathway was originally discovered in the yeast and, for decades, yeast has served as a robust model to study ALT. Using yeast as a model, two types of ALT (-dependent and -independent) have been described. Studies in yeast have provided the phenotypic characterization of ALT survivors, descriptions of the proteins involved, and implicated break-induced replication (BIR) as the mechanism responsible for ALT. Nevertheless, many questions have remained, and answering them has required the development of new quantitative methods. In this review we discuss the historic aspects of the ALT investigation in yeast as well as new approaches to investigating ALT, including ultra-long sequencing, computational modeling, and the use of population genetics. We discuss how employing new methods contributes to our current understanding of the ALT mechanism and how they may expand our understanding of ALT in the future.
端粒的非经典延长(ALT)是一种由 10-15%的癌细胞利用的同源重组途径,使细胞在没有端粒酶的情况下维持端粒。该途径最初在酵母中发现,几十年来,酵母一直是研究 ALT 的强大模型。使用酵母作为模型,已经描述了两种 ALT(依赖和不依赖)。在酵母中的研究提供了 ALT 存活者的表型特征描述,涉及的蛋白质描述,并暗示断裂诱导复制(BIR)是 ALT 负责的机制。然而,仍有许多问题尚未解决,需要开发新的定量方法来回答这些问题。在这篇综述中,我们讨论了酵母中 ALT 研究的历史方面,以及研究 ALT 的新方法,包括超长测序、计算建模和群体遗传学的应用。我们讨论了采用新方法如何有助于我们目前对 ALT 机制的理解,以及它们将来如何扩展我们对 ALT 的理解。