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Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation

Author

Listed:
  • Elizabeth M. Kass

    (Developmental Biology Program, Memorial Sloan Kettering Cancer Center)

  • Pei Xin Lim

    (Developmental Biology Program, Memorial Sloan Kettering Cancer Center)

  • Hildur R. Helgadottir

    (Developmental Biology Program, Memorial Sloan Kettering Cancer Center)

  • Mary Ellen Moynahan

    (Memorial Sloan Kettering Cancer Center)

  • Maria Jasin

    (Developmental Biology Program, Memorial Sloan Kettering Cancer Center)

Abstract

The mammary gland undergoes significant proliferative stages after birth, but little is known about how the developmental changes impact DNA double-strand break (DSB) repair. Mutations in multiple genes involved in homology-directed repair (HDR), considered a particularly accurate pathway for repairing DSBs, are linked to breast cancer susceptibility, including BRCA2. Using reporter mice that express an inducible endonuclease, we find that HDR is particularly robust in mammary tissue during puberty and pregnancy, accounting for 34–40% of detected repair events, more than in other tissues examined. Brca2 hypomorphic mutation leads to HDR defects in mammary epithelium during puberty and pregnancy, including in different epithelial lineages. Notably, a similar dependence on Brca2 is observed in other proliferative tissues, including small intestine epithelium. Our results suggest that the greater reliance on HDR in the proliferating mammary gland, rather than a specific dependence on BRCA2, may increase its susceptibility to tumorigenesis incurred by BRCA2 mutation.

Suggested Citation

  • Elizabeth M. Kass & Pei Xin Lim & Hildur R. Helgadottir & Mary Ellen Moynahan & Maria Jasin, 2016. "Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13241
    DOI: 10.1038/ncomms13241
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    Cited by:

    1. Maryam Ghaderi Najafabadi & G. Kenneth Gray & Li Ren Kong & Komal Gupta & David Perera & Huw Naylor & Joan S. Brugge & Ashok R. Venkitaraman & Mona Shehata, 2023. "A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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