Essential Role of BRCA2 in Ovarian Development and Function

Authors:
  • AWAriella Weinberg-Shukron
    Ariella Weinberg-Shukron
  • MRMariana Rachmiel
    Mariana Rachmiel
  • PRPaul Renbaum
    Paul Renbaum
  • SGSuleyman Gulsuner
    Suleyman Gulsuner
  • TWTom Walsh
    Tom Walsh
  • OLOrit Lobel
    Orit Lobel
  • ADAmatzia Dreifuss
    Amatzia Dreifuss
  • ABAvital Ben-Moshe
    Avital Ben-Moshe
  • SZSharon Zeligson
    Sharon Zeligson
  • RSReeval Segel
    Reeval Segel
  • TSTikva Shore
    Tikva Shore
  • RKRachel Kalifa
    Rachel Kalifa
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Abstract
The causes of ovarian dysgenesis remain incompletely understood. Two sisters with XX ovarian dysgenesis carried compound heterozygous truncating mutations in the BRCA2 gene that led to reduced BRCA2 protein levels and an impaired response to DNA damage, which resulted in chromosomal breakage and the failure of RAD51 to be recruited to double-stranded DNA breaks. The sisters also had microcephaly, and one sister was in long-term remission from leukemia, which had been diagnosed when she was 5 years old. Drosophila mutants that were null for an orthologue of BRCA2 were sterile, and gonadal dysgenesis was present in both sexes. These results revealed a new role for BRCA2 and highlight the importance to ovarian development of genes that are critical for recombination during meiosis. (Funded by the Israel Science Foundation and others.)
Funding Information
  • Breast Cancer Research Foundation
  • National Institutes of Health (R35 CA197458)
  • Hassenfeld family to Shaare Zedek Medical Center (Gift)
  • Israel Science Foundation (1353/12, 1788/15)

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