Protein ubiquitin-proteasome (ubiquitin-proteasome) system is the major mechanism responsible for protein degradation in\neukaryotic cell. During spermatogenesis, the replacement of histone by protamine is vital for normal sperm formation, which\nis involved in ubiquitination enzymes expressed in testis. Recently, histone ubiquitin ligases have been shown to play critical\nroles in several aspects of spermatogenesis, such as meiotic sex chromosome inactivation (MSCI), DNA damage response, and\nspermiogenesis. In this review, we highlight recent progress in the discovery of several histone ubiquitin ligases and elaborate\nmechanisms of how these enzymes are involved in these processes through knockout mouse model. Using Huwe1, UBR2, and\nRNF8 as examples, we emphasized the diverse functions for each enzyme and the broad involvement of these enzymes in every\nstage, from spermatogonia differentiation and meiotic division to spermiogenesis; thus histone ubiquitin ligases represent a class\nof enzymes, which play important roles in spermatogenesis through targeting histone for ubiquitination and therefore are involved\nin transcription regulation, epigenetic modification, and other processes essential for normal gametes formation
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