How do small chromosomes know they are small? Maximizing meiotic break formation on the shortest yeast chromosomes

Hajime Murakami* (Corresponding Author), Xiaojing Mu, Scott Keeney* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The programmed formation of DNA double-strand breaks (DSBs) in meiotic prophase I initiates the homologous recombination process that yields crossovers between homologous chromosomes, a prerequisite to accurately segregating chromosomes during meiosis I (MI). In the budding yeast Saccharomyces cerevisiae, proteins required for meiotic DSB formation (DSB proteins) accumulate to higher levels specifically on short chromosomes to ensure that these chromosomes make DSBs. We previously demonstrated that as-yet undefined cis-acting elements preferentially recruit DSB proteins and promote higher levels of DSBs and recombination and that these intrinsic features are subject to selection pressure to maintain the hyperrecombinogenic properties of short chromosomes. Thus, this targeted boosting of DSB protein binding may be an evolutionarily recurrent strategy to mitigate the risk of meiotic mis-segregation caused by karyotypic constraints. However, the underlining mechanisms are still elusive. Here, we discuss possible scenarios in which components of the meiotic chromosome axis (Red1 and Hop1) bind to intrinsic features independent of the meiosis-specific cohesin subunit Rec8 and DNA replication, promoting preferential binding of DSB proteins to short chromosomes. We also propose a model where chromosome position in the nucleus, influenced by centromeres, promotes the short-chromosome boost of DSB proteins.
Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalCurrent Genetics
Issue number3
Early online date18 Feb 2021
Publication statusPublished - 1 Jun 2021

Bibliographical note

This work was supported by NIH grant R35 GM118092 to SK. MSKCC core facilities are supported by NCI Cancer Center Support Grant P30 CA008748.

Data Availability Statement

Not applicable.


  • Meiosis
  • DNA double-strand breaks
  • Recombination
  • Chromosome segregration
  • Chromosome evolution
  • Chromosome structure


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