Professor Junho Lee and his research team at Department of Biolgical sciences have established the first genome map of Alternative Lengthening of Telomeres (ALT). The ALT phenomenon represents an alternative mechanism for maintaining the chromosome end structure known as telomeres, which has been evolutionarily conserved from yeast to humans and exhibits great diversity and complexity. The genome map of ALT has enabled the identification of previously unknown structural variations associated with ALT, providing a crucial foundation for understanding genomic evolution across evolution, aging, and cancer development. Building on their previous multi-omics analyses of ALT, Professor Lee's team has completed a significant piece of work by creating a long-read-based genome map, allowing for a more accurate understanding of ALT.
Telomeres are essential for maintaining chromosome integrity, serving as protective structures at chromosome ends. They prevent the recognition of chromosome breaks and protect genetic information during cell division, sacrificing their length in the process. When telomeres shorten beyond a critical threshold, they lose their protective function, leading to cellular senescence or apoptosis, which, if dysregulated, can result in tumorigenesis. While the conventional mechanism for telomere length maintenance involves the enzyme telomerase, alternative telomere maintenance mechanisms (ALT) have been identified in certain species and cancer cells. This study first discovered Type 1 ALT in Caenorhabditis elegans and subsequently established both Types 1 and 2 ALT in mouse embryonic stem cells, creating the first genome maps of ALT. By integrating long-read sequencing and Hi-C techniques, we characterized unique structural variations specific to ALT, revealing that these variations contribute to genome instability and DNA damage repair. Our findings indicate that ALT is a conserved genomic preservation program across species, highlighting the need to explore its existence in human cancer cells further. This research provides foundational insights into the evolutionary adaptations of telomere structures and their implications in aging and cancer biology.