Haiwei Feng
Zexiong Lin
Jiahuan Zheng
Dongteng Liu
Rui Guo
Junshi Li
Raymond H.W. Li
Ernest H.Y. Ng
Michael S.Y. Huen
P. Jeremy Wang
William S.B. Yeung
Kui Liu
aShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong - Shenzhen Hospital, Shenzhen, 518000, China
bDepartment of Obstetrics and Gynecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China
cDepartment of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, 19104, USA
dSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China
More InformationCorresponding author: E-mail address: miaoli@hku.hk (Miao Li);E-mail address: kliugc@hku.hk (Kui Liu)
Publish Date:2020-08-25
Abstract
Abstract
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.Keywords: Meiosis,
4930432K21Rik,
Recombination,
Ubiquitination
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