Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing organisms. In this study, we have independently identified a novel meiosis protein male meiosis recombination regulator (MAMERR)/4930432K21Rik and showed that it is indispensable for meiosis prophase I progression in male mice. Using super-resolution structured illumination microscopy, we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 complex. We generated a Mamerr-deficient mouse model by deleting exons 3–6 and found that most of Mamerr^−/− spermatocytes were arrested at pachynema and failed to progress to diplonema, although they exhibited almost intact synapsis and progression to the pachytene stage along with XY body formation. Further mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2–binding protein in Mamerr^−/− spermatocytes was only mildly impaired with a partial reduction in double-strand break repair, whereas a substantial reduction in ubiquitination on the autosomal axes and on the XY body appeared as a major phenotype in Mamerr^−/− spermatocytes. We propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and XY chromosomes, and in the absence of MAMERR, the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.

减数分裂是一种专门的细胞分裂，用于在有性繁殖生物中产生单倍体配子。在这项研究中，我们独立地确定了一种新型的减数分裂蛋白雄性减数分裂重组调节剂（MAMERR）/ 4930432K21Rik，并表明它对于雄性小鼠的减数分裂前期I进程是必不可少的。使用超高分辨率结构照明显微镜，我们发现MAMERR在与复制蛋白A和减数分裂特异的OB域/生精相关的22种复合物相同的双链断裂处起作用。我们通过删除外显子3–6生成了Mamerr缺陷的小鼠模型，发现大多数Mamerr ^-/-精母细胞被阻滞在早幼生殖细胞中，尽管其表现出几乎完整的突触并随着XY体的形成而发展到粗线期，但仍未能发展成双胞胎。进一步的机理研究表明，在Mamerr ^-/-精母细胞中DMC1 / RAD51和热休克因子2结合蛋白的募集仅受到轻度损害，双链断裂修复的部分减少，而常染色体上泛素化的实质性减少XY体在Mamerr ^-/-中表现为主要表型精母细胞。我们提出，MAMERR可能通过调节常染色体和XY染色体上关键减数分裂蛋白的泛素化而参与减数分裂前期I进程，在没有MAMERR的情况下，关键减数分裂蛋白的泛素化受到抑制会导致粗线粒体阻滞和细胞死亡。