The E3 ubiquitin ligase Cullin 4A regulates meiotic progression in mouse spermatogenesis Journal Article
| Authors: | Yin, Y.; Lin, C.; Kim, S. T.; Roig, I.; Chen, H.; Liu, L.; Veith, G. M.; Jin, R. U.; Keeney, S.; Jasin, M.; Moley, K.; Zhou, P.; Ma, L. |
| Article Title: | The E3 ubiquitin ligase Cullin 4A regulates meiotic progression in mouse spermatogenesis |
| Abstract: | The Cullin-RING ubiquitin-ligase CRL4 controls cell cycle and DNA damage checkpoint response and ensures genomic integrity. Inactivation of the Cul4 component of the CRL4 E3 ligase complex in Caenorhabditis elegans by RNA interference results in massive mitotic DNA re-replication in the blast cells, largely due to failed degradation of the DNA licensing protein, CDT-1, and premature spermatogenesis. Here we show that inactivation of Cul4a by gene-targeting in mice only affected male but not female fertility. This male infertility phenotype resulted from a combination of decreased spermatozoa number, reduced sperm motility and defective acrosome formation. Agenesis of the mutant germ cells was accompanied by increased cell death in pachytene/diplotene cells with markedly elevated levels of phospho-p53 and CDT-1. Despite apparent normal assembly of synaptonemal complexes and DNA double strand break repair, dissociation of MLH1, a component of the late recombination nodule, was delayed in Cul4a-/- diplotene spermatocytes, which potentially led to subsequent disruptions in meiosis II and spermiogenesis. Together, our study revealed an indispensable role for Cul4a during male germ cell meiosis. © 2011 Elsevier Inc. |
| Keywords: | controlled study; unclassified drug; nonhuman; protein function; animal cell; mouse; pachytene; phenotype; spermatocyte; synaptonemal complex; meiosis; animal tissue; cell death; gene targeting; mus; dna repair; germ cell; cell protein; cell type; dna strand breakage; double stranded dna; caenorhabditis elegans; ubiquitin protein ligase e3; protein mlh1; cullin 4a; male infertility; spermatozoon count; spermatozoon motility; spermatogenesis; cullin4; mlh1; phospho p53 protein; replication licensing factor cdt1; acrosome; agenesis; diplotene cell |
| Journal Title: | Developmental Biology |
| Volume: | 356 |
| Issue: | 1 |
| ISSN: | 0012-1606 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2011-08-01 |
| Start Page: | 51 |
| End Page: | 62 |
| Language: | English |
| DOI: | 10.1016/j.ydbio.2011.05.661 |
| PROVIDER: | scopus |
| PMCID: | PMC3130830 |
| PUBMED: | 21624359 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "CODEN: DEBIA" - "Source: Scopus" |
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