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Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30

Pei-Ching Huang1,2,3, Soogil Hong4, Hasan F Alnaser5

  • 1Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY, 10021, USA.

The EMBO Journal
|November 29, 2024
PubMed

Insights

The SWI/SNF-like ATPase Fun30 is crucial for DNA double-strand break (DSB) resection during meiosis in yeast. Loss of Fun30 severely impairs resection, impacting homologous recombination and chromosome segregation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA double-strand breaks (DSBs) require nucleolytic processing for homologous recombination.
  • In yeast meiosis, DSB resection involves the MRX complex and Exo1.
  • The role of chromatin remodeling in meiotic DSB resection was previously unknown.

Purpose of the Study:

  • To identify the chromatin remodeler involved in meiotic DSB resection.
  • To elucidate the function of Fun30 in DSB repair pathways.
  • To understand the relationship between resection length and meiotic recombination.

Main Methods:

  • Yeast genetics (mutant analysis: fun30, exo1-nd, double mutants).
  • Chromatin immunoprecipitation to assess protein association with DSBs.
  • Analysis of resection tract lengths and homologous recombination outcomes.

Main Results:

  • The SWI/SNF-like ATPase Fun30 plays a major, nonredundant role in meiotic resection.
  • fun30 mutations significantly shorten resection tracts, comparable to exo1-nd mutations.
  • Fun30 associates with chromatin at DSBs, suggesting a role in nucleosome removal.
  • fun30 exo1-nd double mutants exhibit severely compromised resection, reduced interhomolog recombination bias, and chromosome segregation defects.

Conclusions:

  • Fun30 is essential for both MRX- and Exo1-dependent steps in meiotic DSB resection.
  • Fun30 likely promotes resection by remodeling nucleosomes at DSBs.
  • Minimal resection length is critical for proper homologous recombination and chromosome segregation during meiosis.
Keywords:
Exo1Fun30MeiosisRecombinationResection

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