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A research group from the Institute of Molecular Embryology and Genetics at Kumamoto University, Japan has discovered a gene, “C19ORF57”, that plays a critical role in meiosis. The gene appears to be related to the cause of male infertility and could be a big step forward for reproductive medicine.

 

Meiosis is a specialized cell division that generates sperm or egg. During Meiosis, genetic information is exchanged between maternal and paternal chromosomes by meiotic recombination, which gives genetic differences to the next generation.

Meiotic recombination is initiated by introducing DNA breaks as a normal process.

However, DNA break is nothing less than DNA damage that is a threat to the cell.

Although introduction of DNA breaks is a normal and necessary process to trigger meiotic recombination, such DNA break must be repaired immediately.

In this study, Drs. Ishiguro and Takemoto discovered a novel gene that plays a crucial role in such repairing of DNA damage during meiotic recombination.

 

Previously, the same group discovered Meiosin gene, that acts as the switch that turns on meiosis, the special type of cell division that creates eggs and sperm, and this includes the turning-on of hundreds of other genes in the process. However, the functions of those genes have not yet been fully elucidated. “C19ORF57” gene was one of those genes controlled by MEIOSIN, but its function was unknown.

 

Recently, they set out to assess “C19ORF57” gene to clarify its role in meiosis. Notably, using mass spectrometry, the group was able to find that “C19ORF57” binds to Breast cancer suppressor BRCA2 that is well known to play a role in repairing damaged DNA.

This data suggest C19ORF57 and BRCA2 function together in germ cells.

They further found another evidence showing the cooperation between C19ORF57 and BRCA2. The microscopic imaging demonstrated that C19ORF57 comes to DNA damage sites first, and recruits BRCA2 to the same place on the chromosomes. 

 

In animal experiments using genome editing technology, the researchers found that male mice became infertile if the Meiosin gene was artificially inhibited. Further analysis of the mouse male gonads clarified that the gene plays an essential role in repairing damaged DNA. The newly identified C19ORF57, together with breast cancer suppressor BRCA2 works in this DNA damage repair during meiotic recombination, and appears to be involved with male infertility.

 

There are many cases of human male infertility where the cause is unknown; this finding potentially reveals a new pathology. Even though these experiments were performed on animal models, the C19ORF57 gene is present in humans.  Therapies and diagnosis developed from this research could ensure meiosis quality and decrease the instances of these complications.

 

Figure1  Genetic information is exchanged between maternal and paternal chromosomes by meiotic recombination

 

Figure2　A mechanism of DNA damage repair during meiotic recombination

 

Figure3　 Inhibition of the C19ORF57 gene causes male specimens to become infertile
Reproductive medicine researchers from Kumamoto University (Japan) performed genome editing experiments to verify that the C19ORF57 gene was essential for meiotic recombination. When they removed the gene in a murine experimental model, meiotic recombination was not complete and sperms were not produced making the male animals infertile.