RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females.
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.
Kuznetsov
Sergey
S
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Pellegrini
Manuela
M
Shuda
Kristy
K
Fernandez-Capetillo
Oscar
O
Liu
Yilun
Y
Martin
Betty K
BK
Burkett
Sandra
S
Southon
Eileen
E
Pati
Debananda
D
Tessarollo
Lino
L
West
Stephen C
SC
Donovan
Peter J
PJ
Nussenzweig
Andre
A
Sharan
Shyam K
SK
D000483:Alleles; D000818:Animals; D002842:Chromatids / Q000235:genetics*; D002869:Chromosome Aberrations; D045566:DNA, Cruciform / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D007246:Infertility / Q000235:genetics; D008297:Male; D049469:Meiotic Prophase I / Q000235:genetics* / Q000502:physiology; D008677:Metaphase / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008957:Models, Genetic; D009865:Oocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010053:Ovary / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011995:Recombination, Genetic; D012737:Sex Factors; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure
D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; C519208:RAD51C protein, mouse; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse