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Preparation of Meiotic Chromosome Spreads from Mouse Oocytes for Assessment of Synapsis and Recombination
Published on: July 18, 2025
The Ddc2/ATRIP checkpoint protein monitors meiotic recombination intermediates
Esther Refolio1, Santiago Cavero, Edyta Marcon
1Instituto de Microbiología Bioquímica, CSIC / University of Salamanca, 37007 Salamanca, Spain.
Journal of Cell Science
|June 23, 2011
Summary
The DNA damage checkpoint protein Ddc2/ATRIP is crucial for monitoring meiotic chromosome metabolism. Its absence disrupts the pachytene checkpoint, leading to faulty gametes and aberrant chromosome segregation during meiosis.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Accurate chromosome segregation during meiosis is vital for producing healthy gametes.
- Meiotic recombination and synapsis defects trigger the pachytene checkpoint to prevent errors.
- The role of DNA damage checkpoint proteins in meiotic surveillance is not fully understood.
Purpose of the Study:
- To investigate the function of the conserved DNA damage checkpoint protein Ddc2/ATRIP in the meiotic pachytene checkpoint.
- To determine Ddc2/ATRIP's localization and regulation during meiosis.
- To elucidate Ddc2/ATRIP's role in sensing meiotic recombination intermediates and signaling.
Main Methods:
- Saccharomyces cerevisiae genetics and mutant analysis (DDC2 deletion).
- Immunofluorescence microscopy to observe Ddc2 localization and foci formation.
- Chromatin immunoprecipitation to identify Ddc2 binding sites.
- Analysis of meiotic progression and gamete viability in DDC2 mutants.
- Comparative analysis in mouse meiotic chromosomes.
Main Results:
- Ddc2/ATRIP deletion bypasses the pachytene checkpoint arrest in mutants with meiotic defects, causing faulty meiotic products.
- Ddc2 protein production increases during meiotic prophase and localizes to chromosomal foci at DNA double-strand break (DSB) sites.
- Ddc2 foci formation depends on Spo11-induced DSBs and RPA, indicating sensing of recombination intermediates.
- Pachytene checkpoint signaling is impaired in ddc2 mutants.
- Mammalian ATRIP colocalizes with ATR, TopBP1, and RPA at unsynapsed meiotic chromosomes.
Conclusions:
- Ddc2/ATRIP is a key component of the meiotic surveillance network, monitoring chromosome metabolism.
- Ddc2/ATRIP functions in sensing meiotic DSBs and regulating the pachytene checkpoint.
- The role of Ddc2/ATRIP in meiotic chromosome monitoring is evolutionarily conserved from yeast to mammals.
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