RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females

J Cell Biol. 2007 Feb 26;176(5):581-92. doi: 10.1083/jcb.200608130. Epub 2007 Feb 20.


RAD51C is a member of the RecA/RAD51 protein family, which is known to play an important role in DNA repair by homologous recombination. In mice, it is essential for viability. Therefore, we have generated a hypomorphic allele of Rad51c in addition to a null allele. A subset of mice expressing the hypomorphic allele is infertile. This infertility is caused by sexually dimorphic defects in meiotic recombination, revealing its two distinct functions. Spermatocytes undergo a developmental arrest during the early stages of meiotic prophase I, providing evidence for the role of RAD51C in early stages of RAD51-mediated recombination. In contrast, oocytes can progress normally to metaphase I after superovulation but display precocious separation of sister chromatids, aneuploidy, and broken chromosomes at metaphase II. These defects suggest a possible late role of RAD51C in meiotic recombination. Based on the marked reduction in Holliday junction (HJ) resolution activity in Rad51c-null mouse embryonic fibroblasts, we propose that this late function may be associated with HJ resolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Chromatids / genetics*
  • Chromosome Aberrations
  • DNA, Cruciform / metabolism
  • DNA-Binding Proteins
  • Female
  • Infertility / genetics
  • Male
  • Meiotic Prophase I / genetics*
  • Meiotic Prophase I / physiology
  • Metaphase / genetics*
  • Metaphase / physiology
  • Mice
  • Models, Genetic
  • Oocytes / cytology
  • Oocytes / metabolism
  • Oocytes / ultrastructure
  • Ovary / cytology
  • Ovary / metabolism
  • Ovary / ultrastructure
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism
  • Rad51 Recombinase / physiology*
  • Recombination, Genetic*
  • Sex Factors
  • Spermatocytes / cytology
  • Spermatocytes / metabolism
  • Spermatocytes / ultrastructure
  • Testis / cytology
  • Testis / metabolism
  • Testis / ultrastructure


  • DNA, Cruciform
  • DNA-Binding Proteins
  • RAD51C protein, mouse
  • Rad51 Recombinase
  • Rad51 protein, mouse