Alternative Lengthening of Telomeres in Yeast: Old Questions and New Approaches

Kendra Musmaker, Jacob Wells, Meng Chia Tsai, Josep M. Comeron, Anna Malkova

Research output: Contribution to journalArticlepeer-review


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 Saccharomyces cerevisiae and, for decades, yeast has served as a robust model to study ALT. Using yeast as a model, two types of ALT (RAD51-dependent and RAD51-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.

Original languageEnglish (US)
Article number113
Issue number1
StatePublished - Jan 2024
Externally publishedYes


  • ALT frequency
  • ALT intermediates
  • alternative lengthening of telomeres (ALT)
  • break-induced replication (BIR)
  • Oxford nanopore sequencing technology (ONT)
  • yeast

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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