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Updated: Jun 23, 2025
Serial Enrichment of Spermatogonial Stem and Progenitor Cells SSCs in Culture for Derivation of Long-term Adult Mouse SSC Lines
Published on: February 25, 2013
MRE11 is essential for the long-term viability of undifferentiated spermatogonia
Zhenghui Tang1,2, Zhongyang Liang1,2, Bin Zhang1,2
1Key Laboratory of Reproductive Genetics (Ministry of Education), Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract:
In the meiotic prophase, programmed SPO11-linked DNA double-strand breaks (DSBs) are repaired by homologous recombination (HR). The MRE11-RAD50-NBS1 (MRN) complex is essential for initiating DNA end resection, the first step of HR. However, residual DNA end resection still occurs in Nbs1 knockout (KO) spermatocytes for unknown reasons. Here, we show that DNA end resection is completely abolished in Mre11 KO spermatocytes. In addition, Mre11 KO, but not Nbs1 KO, undifferentiated spermatogonia are rapidly exhausted due to DSB accumulation, proliferation defects, and elevated apoptosis. Cellular studies reveal that a small amount of MRE11 retained in the nucleus of Nbs1 KO cells likely underlies the differences between Mre11 and Nbs1 KO cells. Taken together, our study not only demonstrates an irreplaceable role of the MRE11 in DNA end resection at SPO11-linked DSBs but also unveils a unique function of MRE11 in maintaining the long-term viability of undifferentiated spermatogonia.
Insights
The MRE11-RAD50-NBS1 complex is crucial for DNA repair. This study reveals MRE11
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Programmed DNA double-strand breaks (DSBs) during meiosis are repaired by homologous recombination (HR).
- The MRE11-RAD50-NBS1 (MRN) complex initiates DNA end resection, a critical HR step.
- Residual resection in Nbs1 knockout (KO) cells suggests other factors may be involved.
Purpose of the Study:
- To investigate the role of MRE11 in DNA end resection and homologous recombination.
- To elucidate the function of MRE11 in maintaining spermatogonial viability.
- To compare the cellular consequences of Mre11 versus Nbs1 deficiency.
Main Methods:
- Generation and analysis of Mre11 and Nbs1 knockout mouse models.
- Assessment of DNA end resection and DSB repair in spermatocytes.
- Evaluation of spermatogonial proliferation, apoptosis, and MRE11 nuclear retention.
Main Results:
- DNA end resection was completely abolished in Mre11 KO spermatocytes.
- Mre11 KO spermatogonia exhibited rapid exhaustion due to DSB accumulation, proliferation defects, and apoptosis.
- Nbs1 KO cells retained some nuclear MRE11, explaining incomplete resection and less severe phenotypes compared to Mre11 KO.
Conclusions:
- MRE11 plays an indispensable role in DNA end resection at SPO11-linked DSBs.
- MRE11 has a unique function in preserving the long-term viability of undifferentiated spermatogonia.
- Differences between Mre11 and Nbs1 KO phenotypes are attributed to residual MRE11 in Nbs1 KO cells.
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