ZIP4H (TEX11) deficiency in the mouse impairs meiotic double strand break repair and the regulation of crossing over Journal Article


Authors: Adelman, C. A.; Petrini, J. H. J.
Article Title: ZIP4H (TEX11) deficiency in the mouse impairs meiotic double strand break repair and the regulation of crossing over
Abstract: We have recently shown that hypomorphic Mre11 complex mouse mutants exhibit defects in the repair of meiotic double strand breaks (DSBs). This is associated with perturbation of synaptonemal complex morphogenesis, repair and regulation of crossover formation. To further assess the Mre11 complex's role in meiotic progression, we identified testis-specific NBS1-interacting proteins via two-hybrid screening in yeast. In this screen, Zip4h (Tex11), a male germ cell specific X-linked gene was isolated. Based on sequence and predicted structural similarity to the S. cerevisiae and A. thaliana Zip4 orthologs, ZIP4H appears to be the mammalian ortholog. In S. cerevisiae and A. thaliana, Zip4 is a meiosis-specific protein that regulates the level of meiotic crossovers, thus influencing homologous chromosome segregation in these organisms. As is true for hypomorphic Nbs1 (Nbs1ΔB/ΔB) mice, Zip4h -/Y mutant mice were fertile. Analysis of spermatocytes revealed a delay in meiotic double strand break repair and decreased crossover formation as inferred from DMC1 and MLH1 staining patterns, respectively. Achiasmate chromosomes at the first meiotic division were also observed in Zip4h -/Y mutants, consistent with the observed reduction in MLH1 focus formation. These results indicate that meiotic functions of Zip4 family members are conserved and support the view that the Mre11 complex and ZIP4H interact functionally during the execution of the meiotic program in mammals. © 2008 Adelman, Petrini.
Keywords: controlled study; unclassified drug; dna binding protein; gene sequence; genetics; dna-binding proteins; nonhuman; protein localization; proteins; cell cycle protein; animal cell; mouse; spermatocyte; synaptonemal complex; animal; cytology; meiosis; metabolism; mouse mutant; mammalia; animals; cell cycle proteins; mice; mice, knockout; spermatocytes; mre11 protein; animal tissue; gene targeting; mus; dna repair; nuclear protein; germ cell; animal experiment; animal model; mice, mutant strains; protein; genetic association; morphogenesis; protein interaction; mice, inbred c57bl; physiology; c57bl mouse; nibrin; nuclear proteins; saccharomyces cerevisiae; nucleotide sequence; staining; dna breaks, double-stranded; dna repair enzymes; double stranded dna break; x chromosome; gene control; protein deficiency; polydeoxyribonucleotide synthase; two hybrid system; protein mlh1; testis; mutant; chromosome segregation; two-hybrid system techniques; crossing over; crossing over, genetic; arabidopsis; spermatogenesis; nucleic acid binding protein; dmc1 protein; zip4h protein; mre11a protein, mouse; nijmegen breakage syndrome 1 protein, mouse; tex11 protein, mouse; gene isolation; arabidopsis thaliana
Journal Title: PLoS Genetics
Volume: 4
Issue: 3
ISSN: 1553-7390
Publisher: Public Library of Science  
Date Published: 2008-01-01
Start Page: e1000042
Language: English
DOI: 10.1371/journal.pgen.1000042
PUBMED: 18369460
PROVIDER: scopus
PMCID: PMC2267488
DOI/URL:
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "Molecular Sequence Numbers: GENBANK: AK082794, NM_031276, NM_031384;" - "Source: Scopus"
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MSK Authors
  1. John Petrini
    76 Petrini