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The Pif1 helicase is actively inhibited during meiotic recombination which restrains gene conversion tract length

Dipti Vinayak Vernekar1, Giordano Reginato2,3, Céline Adam1

  • 1Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3244, Dynamics of Genetic Information, Paris, France.

Nucleic Acids Research
|April 6, 2021
PubMed

Insights

The Mer3-MutLβ complex restrains Pif1 DNA helicase activity during meiosis, preventing long gene conversion tracts. This mechanism ensures shorter conversion tracts in meiosis compared to mitosis, potentially reducing associated mutagenesis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Meiotic recombination is crucial for accurate chromosome segregation and generates gene conversion events.
  • Meiotic conversion tracts are typically shorter than mitotic ones due to regulatory mechanisms.
  • The Mer3 helicase and MutLβ heterodimer form a complex that binds meiotic recombination intermediates, but its inhibited targets were unclear.

Purpose of the Study:

  • To identify the molecular actors inhibited by the Mer3-MutLβ complex during meiotic recombination.
  • To elucidate the mechanism by which meiotic conversion tract length is regulated.
  • To investigate the role of Pif1 DNA helicase in meiotic DNA repair synthesis.

Main Methods:

  • Recruitment of Pif1 to meiotic double-strand break (DSB) sites was assessed.
  • The requirement of Pif1 for long gene conversions in the absence of MutLβ was examined.
  • In vitro assays were performed to study the interaction between Mer3-MutLβ, Pif1, DNA polymerase delta (Pol δ), and RFC-PCNA.

Main Results:

  • Pif1 is recruited genome-wide to meiotic DSB sites.
  • Pif1, via PCNA interaction, is essential for long gene conversions when MutLβ is not recruited.
  • The Mer3-MutLβ complex inhibits Pif1-stimulated D-loop extension by Pol δ and RFC-PCNA, possibly by competing for RFC-PCNA binding.

Conclusions:

  • The Mer3-MutLβ complex restrains Pif1's DNA repair synthesis activity during meiosis.
  • This restraint by Mer3-MutLβ prevents long gene conversion tracts, contributing to shorter tracts in meiosis.
  • The findings reveal a mechanism for regulating meiotic recombination tract length and potentially associated mutagenesis.

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