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


Authors: Kass, E. M.; Lim, P. X.; Helgadottir, H. R.; Moynahan, M. E.; Jasin, M.
Article Title: Robust homology-directed repair within mouse mammary tissue is not specifically affected by Brca2 mutation
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. © The Author(s) 2016.
Keywords: mus
Journal Title: Nature Communications
Volume: 7
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2016-10-25
Start Page: 13241
Language: English
DOI: 10.1038/ncomms13241
PROVIDER: scopus
PUBMED: 27779185
PMCID: PMC5093336
DOI/URL:
Notes: Article -- Export Date: 2 November 2016 -- Source: Scopus
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MSK Authors
  1. Mary Ellen Moynahan
    105 Moynahan
  2. Maria Jasin
    250 Jasin
  3. Elizabeth M Kass
    13 Kass
  4. Pei Xin   Lim
    6 Lim