Cul4A is essential for spermatogenesis and male fertility

Dragana Kopanja, Nilotpal Roy, Tanya Stoyanova, Rex A. Hess, Srilata Bagchi, Pradip Raychaudhuri

Research output: Contribution to journalArticlepeer-review

Abstract

The mammalian Cul4 genes, Cul4A and Cul4B, encode the scaffold components of the cullin-based E3 ubiquitin ligases. The two Cul4 genes are functionally redundant. Recent study indicated that mice expressing a truncated CUL4A that fails to interact with its functional partner ROC1 exhibit no developmental phenotype. We generated a Cul4A-/- strain lacking exons 4-8 that does not express any detectable truncated protein. In this strain, the male mice are infertile and exhibit severe deficiencies in spermatogenesis. The primary spermatocytes are deficient in progression through late prophase I, a time point when expression of the X-linked Cul4B gene is silenced due to meiotic sex chromosome inactivation. Testes of the Cul4A-/- mice exhibit extensive apoptosis. Interestingly, the pachytene spermatocytes exhibit persistent double stranded breaks, suggesting a deficiency in homologous recombination. Also, we find that CUL4A localizes to the double stranded breaks generated in pre-pachytene spermatocytes. The observations identify a novel function of CUL4A in meiotic recombination and demonstrate an essential role of CUL4A in spermatogenesis.

Original languageEnglish (US)
Pages (from-to)278-287
Number of pages10
JournalDevelopmental Biology
Volume352
Issue number2
DOIs
StatePublished - Apr 15 2011

Keywords

  • Cul4A
  • Homologous recombination
  • Spermatogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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