Dataset Information

Evolutionarily-conserved MZIP2 is essential for crossover formation in mammalian meiosis.

ABSTRACT: During meiosis, formation of crossovers-the physical links that ensure the segregation of homologous chromosomes-requires a group of evolutionarily conserved ZMM proteins. In budding yeast, three ZMM proteins, Zip2, Spo16, and Zip4, form a trimeric complex to bind recombination intermediates and promote crossover formation. Here, we show that MZIP2 is the mammalian ortholog of Zip2. Complete ablation of MZIP2 in mice caused sterility in both males and females, as well as defects in repairing meiotic DNA double-strand breaks. MZIP2 forms discrete foci on chromosomes axes, and is required for the localization of TEX11 (mammalian Zip4 ortholog) and another ZMM protein, MSH4, to form crossover-prone recombination intermediates. As a consequence, formation of crossovers is abolished and formation of synaptonemal complex is incomplete in MZIP2-null meiocytes, resulting in meiosis arrest at a zygotene-like stage. Our results suggest that the processing of early recombination intermediates toward mature crossovers is dependent on MZIP2.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC6155065 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evolutionarily-conserved MZIP2 is essential for crossover formation in mammalian meiosis.

Zhang Qianting Q Shao Jingchen J Fan Heng-Yu HY Yu Chao C

Communications biology 20180921

During meiosis, formation of crossovers-the physical links that ensure the segregation of homologous chromosomes-requires a group of evolutionarily conserved ZMM proteins. In budding yeast, three ZMM proteins, Zip2, Spo16, and Zip4, form a trimeric complex to bind recombination intermediates and promote crossover formation. Here, we show that MZIP2 is the mammalian ortholog of Zip2. Complete ablation of MZIP2 in mice caused sterility in both males and females, as well as defects in repairing mei ...[more]

PMID: 30272023

Similar Datasets

Project description:Chromosome segregation errors during meiosis result in the formation of aneuploid gametes and are the leading cause of pregnancy loss and birth defects in humans. Proper chromosome segregation requires pairwise associations of maternal and paternal homologous chromosomes. Chiasmata, which are the cytological manifestations of crossovers (COs), provide a physical link that holds the homologs together as a pair, facilitating their orientation on the spindle at meiosis I. Although CO-promoting activities ensure a balanced number and position of COs, their identity and mechanism of action in mammals remain understudied. Previous work in yeast and Arabidopsis has shown that Zip2 and Shoc1 are ortholog proteins with an important role in promoting the formation of COs. Our work is the first study in mammals showing the in vivo and in vitro function of mouse and human SHOC1. We show that purified recombinant human SHOC1, an XPF/MUS81 family member, preferentially binds branched DNA molecules but apparently lacks in vitro endonuclease activity, despite its conserved ERCC4-(HhH)2 core structure. Cytological observations suggest that initial steps of recombination are normal in a majority of spermatocytes from SHOC1 hypomorphic mice. However, late stages of recombination appear abnormal, as chromosomal localization of MLH1 is reduced. In agreement, chiasma formation is reduced, and cells arrest at metaphase I with a few lagging chromosomes and subsequent apoptosis. This analysis of SHOC1-deficient mice and the selective localization of SHOC1 to a subset of recombination sites show that SHOC1 acts at key mid-stage steps of the CO formation process. The formation of chromosome axial elements and homologous pairing are apparently normal, but synapsis is altered with SYCP1 frequently failing to extend the full length of the chromosome axes. Finally, we describe that SHOC1 interacts with TEX11, another protein important for the formation of COs, connecting SHOC1 to chromosome axis and structure.

Dataset Information

Evolutionarily-conserved MZIP2 is essential for crossover formation in mammalian meiosis.

Publications

Evolutionarily-conserved MZIP2 is essential for crossover formation in mammalian meiosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets