The Role Of Morc2b In Mouse Meiosis And Its Mechanism

Sexual reproduction requires the formation of haploid gametes (sperm and egg), and the diploid karyotype is restored after fertilization. Meiosis is a special form of cell division that is distinguished from mitosis. During meiosis, DNA replicates once, but cells divide twice, resulting in production of haploid gamates. During Meiosis I, homologous chromosomes form synapsis mediated by synaptonemal complexes and undergo meiotic recombination (also called crossover) between non-sister chromatids.In meiosis, recombination is necessary for the exchange of genetic material between paternal and maternal chromosomes, which depends on the DNA repair. In the pachytene stage of meiosis I, the synaptonemal complexes are formed, and the damage of DNA is repaired. DNA double strand breaks (DSBs) are formed by Spol 1. DSB repair is facilitated by single-stranded DNA-binding proteins such as RPA, RAD51, DMC1 and MEIOB. RPA interacts with MEIOB/SPATA22 complex. The MEIOB/SPATA22 complex has been hypothesized to capture the second end of the DSB, which eventually leads to the double Holliday junction formation.MORC2B contains a histidine kinase-like ATPase domain and a CW-type zinc finger. These domains are associated with DNA transcription and repair. In our experimental results, the Morc2b-null mice exhibit a failure in chromosomal synapsis and meiotic recombination. There is a so-called pachytene checkpoint in early stage of meiosis I. Because of the failure in chromosomal synapsis, meiosis is arrested early due to the meiotic checkpoint. As a result, both Morc2b-nvll males and females are sterile.MORC1, MORC2A, and MORC2B all belong to the MORC protein family. Among them, MORC2B is only present in rodents (mouse and rat). In addition, MORC2B is only expressed in testis. Our results show that MORC1, MORC2A, and MORC2B proteins interact with each other and each of them interacts with themselves, forming homodimers. MORC2B is mainly present in spermatocytes and round spermatids. MORC2B is a nuclear protein but is not detected on chromosomes in spermatocytes. MORC1, MORC2A, and MORC2B may indirectly affect the DNA repair during meiosis. Our experimental results show that Morc2b is required for mouse meiosis and fertility.