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Chromatin Spread Preparations for the Analysis of Mouse Oocyte Progression from Prophase to Metaphase II
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Published on: February 26, 2018

A mammalian-specific domain of MSH5 drives the transition from crossover licensing to designation during meiotic

Ky'ara D Carr1, Eliza O'Donnell1, Tegan S Horan1

  • 1Department of Biomedical Sciences and Cornell Reproductive Sciences Center (CoRe), Cornell University, Ithaca, NY 14853.

Biorxiv : the Preprint Server for Biology
|June 29, 2026
PubMed

Insights

The MSH5 C-terminus is crucial for proper crossover (CO) patterning during meiosis. Its loss disrupts the coordination of key proteins, leading to germ cell death and uncoupling of CO regulation.

Area of Science:

  • Genetics
  • Cell Biology
  • Reproductive Biology

Background:

  • Meiotic recombination involves DNA double-strand breaks (DSBs) repaired as crossovers (COs) or non-crossovers.
  • MSH4/MSH5 (MutSγ) licenses DSB repair intermediates, directing them to the class I CO pathway via MLH1/MLH3 (MutLγ).
  • Mammalian MSH4/MSH5 may also direct repair through the class II CO pathway, suggesting additional functions.

Purpose of the Study:

  • To investigate the role of the mammalian-specific 38-amino acid C-terminal domain of MSH5.
  • To understand how the MSH5 C-terminus influences CO pathway selection and regulation.

Main Methods:

  • Utilized mice lacking the MSH5 C-terminal domain (Msh5ΔC/ΔC).
  • Analyzed spermatocytes and oocytes for MSH4 loading, MutLγ foci, and associated factors (HEI10, CNTD1, RNF212B, CDK4, CDK2).
  • Assessed germ cell viability and progression through prophase I.

Main Results:

  • MSH4 loading occurred normally, but MSH4 levels declined in pachynema in Msh5ΔC/ΔC mice.
  • MutLγ foci and pro-CO factors HEI10 and CNTD1 were significantly reduced.
  • The switch from licensing-associated CDK4 to CO-site-associated CDK2 failed, leading to rapid germ cell death.

Conclusions:

  • The MSH5 C-terminus is essential for the stepwise patterning of class I COs by regulating key proteins.
  • Loss of the MSH5 C-terminus uncouples regulatory proteins, disrupting CO pathway progression.
  • Novel early roles for the MSH5 C-terminus in converting licensed DSB intermediates to class I COs were revealed.
Keywords:
CDK2CDK4Meiotic recombinationMutSγcrossoversdesignationlicensing

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